Dr. T. Rajkumar

CURRICULUM VITAE

1. NAME IN FULL: THANGARAJAN RAJKUMAR

2. DATE OF BIRTH: 30-11-1957

3. ADDRESS & DESIGNATION:

a) Present: Professor and Head, Dept. of Molecular Oncology,

Cancer Institute (WIA), Adyar, Madras - 600020, India.

Phone: 2350131; 2350241. Fax: 4912085

Email: moc.lnsv|aiw_etutitsni_recnac#moc.lnsv|aiw_etutitsni_recnac

2. Permanent: as above

4. PROFESSIONAL QUALIFICATIONS:

DEGREE SUBJECT INSTITUTION/UNIVERSITY DURATION

MBBS Medicine Madras Medical College, 1975-1982

Madras - 600003, India.

University of Madras.

M.D. General Medicine Madras Medical College, 1982-1985

Madras - 600003, India.

University of Madras.

D.M. Medical Oncology Cancer Institute (WIA), 1986-1988

Adyar, Madras - 600020

University of Madras.

Ph.D. Science Royal Postgraduate Medical School, 1991-1994

(Molecular Oncology) Hammersmith Hospital, London, UK.

University of London.

HONOURS

1. First qualified Medical Oncologist with a Ph.D. in Basic Science (Molecular Oncology) in India.

2. Visiting Professor, Dept. of Clinical Oncology, RPMS and Hammersmith Hospital, London, UK.

Tamilnadu Medical Council Registration No: 35442
5. POST-GRADUATE TRAINING/EXPERIENCE
FROM TO NAME OF ORGANISATION AND NATURE OF TRAINING
16-07-85 15-01-86 Cancer Chemotherapy Dept., Govt. Royapettah Hospital,

Special Trainee
01-04-86 31-03-88 Post-graduate in Medical Oncology, Cancer Institute, Adyar
07-10-91 31-10-94 Research Fellow, ICRF Molecular Oncology Unit, Hammersmith Hospital, London, UK.

APPOINTMENTS HELD

02-10-08 – till date. Professor and Head, Dept. of Molecular Oncology, Cancer Institute (WIA).

01-06-2006 till 01-10-08. Director and Scientific Director, & Professor and Head, Dept. of Molecular Oncology, Cancer Institute (WIA). (Resigned Directorship on 01-10-08).

14-12-2000 -31-05-2006. Scientific Director, Professor and Head, Dept. of Molecular Oncology, Cancer Institute (WIA).

01-04-2000 till 13-12-2000. Director (Laboratories and Research), Chairman, Division of Biological Sciences, Professor and Head, Dept. of Molecular Oncology, Cancer Institute (WIA).

2nd April 1997 -

to 31-03-2000. Deputy Director (Research), Chairman, Division of Biological Sciences, Professor and Head, Dept. of Molecular Oncology, Cancer Institute (WIA).

1st April 1996 -

1st April 1997. Chairman, Division of Biological Sciences (Depts. of Molecular Oncology, Cytogenetics, Immunology/Haematology and Electron Microscopy).

1st December 1994 -

31st March 1996. Professor and Head of the Department of Molecular Oncology, Cancer Institute (WIA) and Muthulakshmi College of Oncological Sciences, Madras, India.

8th October 1991-

26th November 1994. Clinical Research Fellow in the ICRF Molecular Oncology Unit, RPMS, Hammersmith Hospital, London, UK.

1st April 1990 -

30th November 1994. Reader in the Dept. of Medical Oncology, Cancer Institute (WIA) and Muthulakshmi College of Oncological Sciences, Madras, India.

1st April 1988-

31st March 1990. Assistant Professor, Dept. of Medical Oncology, Cancer Institute (WIA) and Muthulakshmi College of Oncological Sciences, Madras, India.

Prizes and Medals and Awards

1. Johnstone Gold Medal - Best outgoing M.B.B.S student.

2. Col.K.G. Pandalai Charitable - Best outgoing M.B.B.S. student.

Trust Endowment Prize

3. Dr. Senthilnathan Gold Medal - Best outgoing male M.B.B.S. student.

4. Dr.J.A.S. Masilamani Memorial - Highest number of marks in all

Gold Medal University examinations

5. Dr.G. Rama Rao Gold Medal - Anatomy

6. Dr. Rajasekara Reddy Prize - Anatomy

7. Dr. K. Govindareddy Memorial - Highest number of University

Gold Medal examination marks in Anatomy

8. Dr. Sundarareddy Memorial - Highest number of University

Prize examination marks in Anatomy

9. Col.Van Geyzel Prize - Biochemistry

10. Dr.Samuel Jesudoss Prize - Pharmacology

11. Bradfield Prize - Highest number of University examination marks in Anatomy and Surgery

12. Certificate of Merit- Physiology - Highest number of University examination marks in Physiology

13. Certificate of Merit- Pharmacology - Highest number of University examination marks in Pharmacology

14. Nutrition Prize - Essay and Elocution

15. Certificate of Honour - Bacteriology

16. Certificate of Honour - Pharmacology

During M.D. (General Medicine)

17. Dr. Edmund Leorde Chalke Prize - Best Post-graduate in Medicine.

Post D.M.

18. Recipient of the Commonwealth Scholarship for 1991, tenable at Royal Postgraduate Medical School, Hammersmith Hospital, London, for Cancer Research.

Post-Doctoral

1. Recipient of the Inventor's Award from Imperial Cancer Research Fund, UK.
2. Elected as a Fellow of the National Academy of Medical Sciences, India (FAMS). - 2007
3. Shri Ramniklal J Kinarivala Cancer Research Award, 2008

PUBLICATIONS:

National: 30

International: 41

LIST OF PUBLICATIONS

1. Krishnamurthy S, Shantha V, Rajkumar T. Drug therapy in oncology - its priority and economics- the Institute experience. Indian Journal of Cancer Chemotherapy, 10: 73-82, 1988.
2. Rajkumar T*, Hemanthraj E, Venkataraman MS, Sukumaran MS and Shantha V. Primary splenic lymphoma with pancreatic involvement - A case report. Indian Journal of Cancer Chemotherapy, 11: 53-55, 1989.
3. Kumar L, Rajkumar T, Raghunath Rao D, Usha Devi CJ, Sagar TG, Shanta V. Intrathecal methotrexate toxicity. JAPI, 37: 351, 1989.
4. Sagar TG, Maitreyan V, Rajkumar T, Maji U and Shantha V. Primary malignant lymphoma of the minor salivary gland - A case report. Indian Journal of Cancer Chemotherapy, 12: 71-73, 1990.
5. Rajkumar K, Rajkumar T, Sagar TG, Maitreyan V and Shantha V. Cryptococcal meningitis in a Hodgkin's lymphoma patient - A case report. JAPI., 40: 707-708, 1991.
6. Shantha V and Rajkumar T. Malignant epithelial tumours of the ovary - concepts in the diagnosis and management. In: Textbook of Obstetrics and Gynaecology for Postgraduates. Orient Longmans, vol 1, 364-380, 1992.
7. Rajkumar T*, Maitreyan V, Sagar TG, Vasanthan A, Shastri DVLN and Shantha V. Germ cell tumour of the ovary - management and results at the Institute. Indian Journal of Cancer, 29: 18-23, 1992.
8. Rajkumar T*, Maitreyan V, Sagar TG, Vasanthan A, Hemanthraj E, Aruna C and Shantha V. Neo-adjuvant chemotherapy in osteosarcoma - a pilot trial. Indian Journal of Cancer, 29: 139-142, 1992.
9. Rajkumar T, Gooden CSR, Lemoine NR and Gullick WJ. Expression of c-erbB3 protein in gastrointestinal tumours as determined by monoclonal antibody RTJ1. J. Pathol., 170: 271-278, 1993.
10. Sanidas EE, Filipe MI, Linehan J, Lemoine NR, Gullick WJ, Rajkumar T and Levison DA. Expression of the c-erbB3 gene product in gastric cancer. Int.J.Cancer, 54: 935-940, 1993.
11. Rajkumar T and Gullick WJ. Type1 growth factor receptors in human breast cancer. Breast Cancer Research and Treatment, 29: 3-9, 1994.
12. Sheikh AA, Sagar TG, Maitreyan V, Rajkumar T, Maji U, Shantha V. Secretory Immunoblastic lymphoma. JAPI, 42: 155-156, 1994.
13. Rajkumar T and Gullick WJ. A monoclonal antibody to the extracellular domain of the human c-erbB3 protein stimulates the growth of breast tumour cell lines. Br J Cancer, 70: 459-465, 1994.
14. Rajkumar T, Maji U, Mallikarjuna VS, Shantha V and Gullick WJ. c-erbB3 expression in cervical tumours as determined by the monoclonal antibody RTJ2. Int J Oncol., 6: 105-109, 1995.
15. Rajkumar T, Hollywood DP, Hurst H and Gullick WJ. c-erbB3 expression in breast tumour derived cell lines. The Breast, 4, 84-91, 1995.
16. Hunt CR, Hale RJ, Armstrong C, Gullick WJ, Rajkumar T, Buckley CH. c-erbB3 proto-oncogene expression in uterine cervical carcinoma. Int. J. Gynaec. Oncol., 5: 282-285, 1995.
17. Rajkumar T and Gullick WJ. The type 1 (EGF receptor) growth factor receptor family and their ligands: their role in human cancers. Waxman, J (ed). Molecular Biology of cancer. Cambridge University Press, Cambridge, 3-14, 1996.
18. Rajkumar T and Gullick WJ. The production of antibodies to growth factor receptors using synthetic peptides as immunogens. Jankowski, J A Z and Polak, J M. (eds). Clinical Gene Analysis and Manipulation: tools, techniques and trouble-shooting. Cambridge University Press, Cambridge, 99-110, 1996.
19. Rajkumar T, Stamp G, Panda H, Waxman J and Gullick WJ. Type 1 growth factor receptors in bladder cancer - An immunohistochemical study. J. Pathol., 179: 381-385, 1996.
20. Nirmala K, Kalaichelvi K, Rajalakshmi KR, Ganapathi Raman S, Van Dongen JJM, Shanta V, Rajkumar T *. TAL-1 deletion in T-cell acute lymphoblastic leukaemia - Implications in the detection of minimal residual disease. Indian J Med and Paed Oncology, 17: 79-84, 1996.
21. Rajkumar T, Stamp G, Hughes CM and Gullick WJ. Immunohistochemical analysis of c-erbB3 protein expression in ovarian carcinomas. J Clin Mol Pathol. 49: M199-M202, 1996.
22. Pushpa V, Raghunathan K, Majhi U, Pandit RV, Shanthi G, Rajkumar T *. Emperipolesis - An electron microscopic characteristic in RDD (Rosai-Dorfman Disease) - A case report. Indian J Med and Paed Oncology, 18, 14-16, 1997.
23. Susheela M, Parameswari E, Rajalakshmi KR, Devarajan S, Shanta V, Rajkumar T* Cytogenetic studies in ALL - Prognostic implications. Ind. J Haemat & Blood Transfusion, 15,11-15, 1997
24. Jayashree B, Deshmukh S, Visalakshi V, Rajalakshmi KR, Sukumaran MS, Moni MS, Rajkumar T *. Proton Magnetic Resonance spectroscopy of murine fibrosarcoma cell lines. Ind J Biochem Biophysics , 35, 108-114, 1998.
25. Rajkumar T *, Sharmila R, Majhi U, Selvaluxmi G, Vasanthan A, Shanta V. Bcl-2 and p53 expression in stage IIB and IIIB cervical cancers. Eur J Gynecol Oncol , 19, 556-560, 1998.
26. Rajkumar T*, Nirmala Nancy K, Selvaluxmi G, Majhi U and Ramanan G. Molecular Studies in cervical cancers and Acute Lymphoblastic Leukemias. Proceedings of the Workshop on Indo-German Collaboration in Oncology: Into the next Millennium. Sponsored by ICMR, New Delhi and Tata Memorial Centre, Mumbai: 8-9, 1999.
27. Rajkumar T*. Pugai namakku pagai. Article on ill effects of Tobacco in Tamil. Dhinakaran.
28. Jayashree B, Deshmukh S, Rajkumar T*. Assessment of human sarcoma tissues by proton NMR spectroscopy: correlation with histopathology. Current Science , 77,(4), 587-592, 1999.
29. Jayashree B, Rajalakshmi KRR, Deshmukh S, Rajkumar T*. Two dimensional NMR spectroscopic study of fibroblast and fibrosarcoma cell lines. Current Science, 77,(5), 706–709, 1999.
30. Rajkumar T*. Environment and Cancer. Hindu , 12-9-99.
31. Rajkumar T * and Vijayalakshmi. Molecular studies in cervical cancer. Proceedings of the XV Asia Pacific Cancer Conference, Published as a Supplementary issue of the Asian and Pacific Journal of Cancer Prevention, 1, 15-17, 2000.
32. Hemanth Raj E, Skinner A, Majhi U, Nirmala K, Ravichandran K, Shanta V, Hurst H, Gullick WJ, Rajkumar T. Neuregulin 1- Alpha Expression In Locally Advanced Breast Cancer. The Breast, 10, 41-45, 2001 .
33. Rajkumar T*. Growth factor and growth factor receptors. Current Science; 81: 535-541, 2001.
34. Nirmala K., Rajalekshmy K. R., G Raman. S., Shanta,V and Rajkumar T. PCR-Heteroduplex analysis of TCR g, d and Tal-1 deletions in T-Acute Lymphoblastic leukemias: Implications in the detection of Minimal Residual Disease. Leukemia Research,Vol.26 (4), 335-43, 2002
35. Vijayalakshmi N, Selvaluxmi G, Mahji U and Rajkumar T*. c-Myc oncoprotein expression and prognosis in patients with carcinoma cervix - An immunohistochemical study”. Eur.J Gynaecol Oncol. 23(2) 135-38, 2002
36. Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nanadakumar A, Gajalakshmi V, Ravichandran K, Ramdas K, Sankaranaray anan R, Munoz N, Franceschi S. Oral cancer in Southern India: the influence of smoking, drinking, paan-chewing and oral hygiene. Int J Cancer, 98, 440-445, 2002.
37. Rajkumar T* and Vijayalakshmi N. Is there a role for surrogate markers of pre-malignant lesions of cervix in India? Proc. Indian Natl Sci Acad. B69 (1), 73-82, 2003.
38. Rajkumar T*. Cancer in the next decade. Reach, 2003.
39. Rajkumar T, Sridhar H, Balaram P, Vaccarella S, Gajalakshmi V, Nanadakumar A, Ramdas K, Munoz N, Herrero R, Franceschi S and Weiderpass E. Oral cancer in Southern India: The influence of body size, diet, infections and sexual practices. Eur. J. Cancer Prevention, 12, 135-143, 2003.
40. Rajkumar T, Franceschi S, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. The role of paan chewing and dietary habits in cervical carcinoma in Chennai, India. Br J Cancer, 88: 1388-1393, 2003.
41. Franceschi S, Rajkumar T, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. Human papilloma virus and risk factors for cervical cancer in Chennai, India: A case control study. Int. J Cancer, 107: 127-133, 2003.
42. Rajkumar T*, Soumittra N, Nirmala Nancy, Swaminathan R, Sridevi V, Shanta V BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prevent. 4: 203-208, 2003.
43. Nirmala Nancy and Rajkumar T* Detection of minimal residual disease in ALL. Lalit Kumar ed., Progress in Haematologic Oncology. The Advanced Research Foundation, New York. 45-60, 2003.
44. Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P, Rajkumar T, Sridhar H, Rose B, Pintos J, Fernandez L, Idris A, Martinez C, Nieto A, Talamini R, Tavani A, Bosch FX, Snijders PJF, Viscidi R, Munoz N, Franceschi S. The viral etiology of oral cancer: evidence from the IARC multicentric study. JNCI. 95:1772-1783, 2003.
45. Rajkumar T*. Molecular mechanisms of cancer. Dr.V.Shanta & Dr.T.Rajkumar ed., Postgraduate Oncology Update, Indian Journal of Clinical Practice, 31-41, 2004.
46. Rajkumar T*. Hereditary cancers. Dr.V.Shanta & Dr.T.Rajkumar ed., Postgraduate Oncology Update, Indian Journal of Clinical Practice, 84-95, 2004.
47. Rajkumar T*, Soumittra N, Durgatosh Pandey, Karunakaran Nirmala Nancy, Vikas Mahajan and Urmila Majhi. Mutation analysis of hMSH2 and hMLH1 in colo-rectal cancer patients in India. Genetic Testing, 8:157-162, 2004.
48. Min Dai, Gary M. Clifford, Florence le Calvez, Xavier Castellsagué, Peter J. F. Snijders, Michael Pawlita, Rolando Herrero, Pierre Hainaut and Silvia Franceschi for the IARC Multicenter Oral Cancer Study Group (In addition to the authors, the following investigators contributed to the study: Nubia Muñoz, IARC, Lyon, France; Javier Pintos, McGill University, Montreal, Canada; Frank Kee, Queen’s University Belfast, Northern Ireland, United Kingdom; Leticia Fernandez, Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba; Chris J. L. M. Meijer, Vrije Universiteit Medical Center, Amsterdam, the Netherlands; Ali Idris, Toombak and Smoking Research Center, Khartoum, the Sudan; María José Sánchez, Escuela Andaluza de Salud Publica, Granada, Spain; Adoracion Nieto, Facultad de Medicina, Sevilla, Spain; F. Xavier Bosch, Institut Català d’Oncologia, Barcelona, Spain; Renato Talamini, Centro di Riferimento Oncologico di Aviano, Aviano, Italy; Alessandra Tavani, Instituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; Ulrich Reidel, Deutsches Krebsforschungszentrum, Heidelberg, Germany; Jolanta Lissowska, Cancer Center, Warsaw, Poland; Barbara Rose, Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney Australia; Hema Sridhar, Kidwai Memorial Institute of Oncology, Bangalore, India; Prabda Balaram, Regional Cancer Center, Trivandrum, India; Thangarajan Rajkumar, Cancer Institute (WIA), Chennai, India; Raphael Viscidi, Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine Baltimore, Maryland). Human Papillomavirus Type 16 and TP53 Mutation in Oral Cancer Matched Analysis of the IARC Multicenter Study. Cancer Res 64, 468-471, 2004.
49. G Gopal and Rajkumar T. Variant of mitochondrial ribosomal protein s28 (mrps28) gene is differentially expressed in response to radiation in a cervical carcinoma derived cell line. Ind J Biochem Biophysics, 42: 81-86, 2005.
50. T. Parija, S. Shirley, S. Uma, K.R Rajalekshmy, S. Ayyappan, T. Rajkumar. Type 1 (11; 22)(q24: q12) translocation is common in Ewing’s sarcoma / PNET in south Indian patients. J Biosciences 30(3), 371-376, 2005.
51. Aimée R. Kreimer , Gary M. Clifford, Peter J.F. Snijders, Xavier Castellsagué, Chris J.L.M. Meijer, Michael Pawlita, Raphael Viscidi, Rolando Herrero, Silvia Franceschi, for the International Agency for Research on Cancer (IARC) Multicenter Oral Cancer Study Group. [The following investigators contributed to the study: Nubia Muñoz, IARC, Lyon, France; Javier Pintos, McGill University, Montreal, Canada; Frank Kee, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom; Leticia Fernández, Instituto Nacional de Oncología y Radiobiología, Havana, Cuba; Ali Idris, Toombak and Smoking Research Center, Khartoum, the Sudan; María José Sánchez, Escuela Andaluza de Salud Pública, Granada, Spain; Adoración Nieto, Facultad de Medicina, Seville, Spain; F. Xavier Bosch, Institut Català d'Oncologia, Barcelona, Spain; Renato Talamini, Centro di Riferimento Oncologico di Aviano, Aviano, Italy; Alessandra Tavani, Instituto di Ricerche Farmacologiche Your browser may not support display of this image.Mario NegriYour browser may not support display of this image., Milan, Italy; Ulrich Reidel, Deutsches Krebsforschungszentrum, Heidelberg, Germany; Jolanta Lissowska, Cancer Center, Warsaw, Poland; Barbara Rose, Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia; Hema Sridhar, Kidwai Memorial Institute of Oncology, Bangalore, India; Prabha Balaram, Regional Cancer Centre, Trivandrum, India; Thangarajan Rajkumar, Cancer Institute (WIA), Chennai, India.] HPV16 semiquantitative viral load and serologic biomarkers in oral and oropharyngeal squamous cell carcinomas. Int J Cancer 115, 329-332, 2005.
52. Rajkumar T*, Gopal G, Selvaluxmi G and K.R.Rajalekshmy. CDC27 is involved in radiation response in squamous cell carcinoma of the cervix. Ind J Biochem Biophysics 45, 271-278, 2005.
53. Rajkumar T*, Soumittra N, Vidubala E, Sridevi V, Mahajan V, Ramanan SG, Vijaya S. Organization and running of the first comprehensive hereditary cancer clinic in India. Hereditary Cancer in Clinical Practice 3(4) pp. 165-170, 2005.
54. International Collaboration of Epidemiological Studies of Cervical cancer [Analysis and writing committee: P Appleby, V Beral, A Berrington de González, D Colin, S Franceschi, J Green, C La Vecchia, J Peto, M Plummer, G Randi, S Sweetland.
Steering committee: FX Bosch, R Herrero, A Hildesheim, C La Vecchia (chairman), D Skegg, D Thomas.
Collaborators: Cancer Institute (WIA), Chennai, India: T Rajkumar; Cancer Research UK Epidemiology Group, Wolfson Institute of Preventive Medicine, London, UK: J Cuzick; Cancer Research UK Epidemiology Unit, Oxford, UK: P Appleby, R Barnabas, V Beral, A Berrington de González, D Bull, K Canfell, B Crossley, J Green, G Reeves, S Sweetland; Danish Cancer Society, Copenhagen, Denmark: S Kjaer; Unit of Health Care Epidemiology, Oxford, UK: R Painter, M Vessey; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA: J Daling, M Madeleine, R Ray, D Thomas; Guanacaste Epidemiological Project, San José, Costa Rica: R Herrero; Department of Medical Epidemiology and Biostatistics, Karolinska Institut, Stockholm, Sweden: N Ylitalo; Epidemiology and Cancer Registration Unit, IDIBELL, Institut Català d'Oncologia, Barcelona, Spain: FX Bosch, S de Sanjosé, X Castellsagué, V Moreno; Institut Nacional de Santé Publique, Algiers, Algeria: D Hammouda; Istituto di Ricerche Farmacologiche Your browser may not support display of this image.Mario NegriYour browser may not support display of this image., Milan, Italy: E Negri, G Randi; Instituto Especializado de Enfermedades Neoplásicas Your browser may not support display of this image.Dr Eduardo Cáceres GrazianiYour browser may not support display of this image., Lima, Peru: M Alvarez, O Galdos, C Santos, C Velarde; International Agency for Research on Cancer, Lyon, France: D Colin, S Franceschi, N Muñoz, M Plummer; London School of Hygiene and Tropical Medicine, London and Institute of Cancer Research, Sutton, UK: J Peto; Lund University, Mälmo, Sweden: J Dillner, I Silins; Ministere de la Santé Publique et des Affaires Sociales, Bamako, Mali: S Bayo; Ministry of Health, Rabat, Morocco: N Chaouki; Ministry of Health, Asunción, Paraguay: PA Rolón; National Cancer Institute, NIH, Bethesda, Maryland, USA: L Brinton, A Hildesheim, J Lacey Jr, M Schiffman; Cancer Epidemiology Research Group, National Health Laboratory Service, Johannesburg, South Africa: L Stein, MI Urban; Royal College of General Practitioners Oral Contraception Study, UK: P Hannaford; Prince of Songkla University, Songkla, Thailand: SB Chichareon; The Cancer Council New South Wales, Sydney, Australia: F Sitas; Universidade de São Paulo, São Paulo, Brazil: J Eluf-Neto; University of Milan, Milan, Italy: C La Vecchia; University of Otago, Dunedin, New Zealand: D Skegg; University of Southern California, Los Angeles, California, USA: R Peters, M Pike, G Ursin; University of the Philippines, Manila, The Philippines: C Ngelangel; University of Tromsø, Tromsø, Norway: IT Gram; World Health Organisation, Geneva, Switzerland: T Farley, O Meirik.]. Cervical carcinoma and reproductive factors: collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies. Int J Cancer. 2006 Sep 1;119(5):1108-24.
55. International Collaboration of Epidemiological Studies of Cervical cancer. Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies. Int J Cancer. 2006 Mar 15;118(6):1481-95.
56. Xavier Castellsagué, Mireia Díaz, Silvia de Sanjosé, Nubia Muñoz, Rolando Herrero, Silvia Franceschi, Rosanna W. Peeling, Rhoda Ashley, Jennifer S. Smith, Peter J. F. Snijders, Chris J. L. M. Meijer, F. Xavier Bosch For the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Worldwide Human Papillomavirus Etiology of Cervical Adenocarcinoma and Its Cofactors: Implications for Screening and Prevention. JNCI Journal of the National Cancer Institute 2006 98(5):303-315. [The IARC Multi-center Cervical Cancer Study Group includes the following additional researchers: M. Plummer (IARC, Lyon), France; V. Moreno (Institut Català d'Oncologia, Barcelona), Spain; P. Alonso de Ruiz (General Hospital of Mexico, Mexico), Mexico; S. Chichareon (Prince of Songkla University, Hat-Yai), Thailand; C. Ngelangel (University of the Philippines, Manila), The Philippines; J. Eluf-Neto (Universidade de Sao Paulo, Sao Paulo), Brazil; P. A. Rolón (Laboratorio de Anatomia Patológica y Citologia, Asunción), Paraguay; E. Caceres and C. Santos (Maes Heller Cancer Research Institute, Lima), Peru; N. Chaouki and B. El Gueddari (Institut National d'Oncologie, Rabat), Morocco; D. Hammouda (Institut National de Santé Publique, Département Contrôle des Maladies, Alger), Algeria; T. Rajkumar (Cancer Institute, Adyar, Chennai), India.]
57. Quint WG, Pagliusi SR, Lelie N, de Villiers EM, Wheeler CM; World Health Organization Human Papillomavirus DNA International Collaborative Study Group. Members of the WHO HPV DNA International Collaborative Study Group are as follows: F.M. Buonaguro, Istituto Nazionale Tumori, Laboratory of Viral Oncology and AIDS, Naples, Italy; R. D. Burk, Cancer Research Center, Albert Einstein College of Medicine, New York, N.Y.; C. Clavel, Laboratoire Pol Bouin, Unite´ de Biologie Cellulaire, Reims, France; J. Cuzick, Cancer Research UK, Department of Epidemiology/Mathematics and Statistics, London, United Kingdom; B. C. Das, M. K. C. G. Medical College, Department of Social and Preventive Medicine, Berhampur, India; J. Dillner, Lund University, Malmo University Hospital, Malmo, Sweden; S. M. Garland, Royal Women’s and Royal Children’s Hospitals, Department of Microbiology and Infectious Diseases, Melbourne, Australia; P. Gravitt, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.; T. Iftner, Universita¨tsklinikum Tuebingen, Institut fur Medizinische Virologie, Tuebingen, Germany; R. Kelkar, Tata Memorial Hospital, Department of Microbiology, Mumbai, India; M. von Knebel Doeberitz, University of Heidelberg, Division of Molecular Diagnostics and Therapy, Heidelberg, Germany; J. Kornegay, Roche Molecular Systems Inc., Alameda, Calif.; A. T. Lorincz, Digene Corporation, Gaithersburg, Md.; B. Lloveras Rubio, Institut Catala` d’Oncolgia, Barcelona, Spain; M.-T. Martin, GlaxoSmithKline, Rixensart, Belgium; C. Meijer, Academic Hospital Veije University, Amsterdam, The Netherlands; J. S. Park, Kangnam St. Mary’s Hospital, Catholic University Medical College, Seoul, Republic of South Korea; S. N. Park, Korea Food and Drug Administration, Division of Viral Products Korea FDA, Seoul, Republic of South Korea; W. Quint, Delft Diagnostic Laboratory, Delft, The Netherlands; T. Rajkumar, Cancer Institute, Department of Molecular Oncology, Chennai, India; R. Sahli, Institut de Microbiologie, Lausanne, Switzerland; L. L. Villa, Instituto Ludwig de Pesquisa sobre o Cancer, Sao Paolo, Brazil; C. Wheeler, University of New Mexico, Department of Molecular Genetics and Microbiology, Albuquerque, N. Mex.; and A. L. Williamson, University of Cape Town, National Health Laboratory Service and Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa. Results of the first World Health Organization international collaborative study of detection of human papillomavirus DNA. J Clin Microbiol. 2006 Feb;44(2):571-9.
58. Sudhakar N, Nancy NK, Rajalekshmy KR, Ramanan G, Rajkumar T. T-cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T-cell acute lymphoblastic leukemia. Am J Hematol. 2007 Mar;82(3):215-21.
59. Uma Ramanathan S. and Rajkumar T*. DNA Microarray and breast cancer – A review. International Journal of Human Genetics.2007, March, 7(1), 49-56.
60. International Collaboration of Epidemiological Studies of Cervical cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007 Feb 15;120(4):885-91.
61. M.Samson, R.Swaminathan, R.Rama, V.Sridevi, K.Nirmala Nancy, T.Rajkumar*. Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and p53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer – A case control study from South India. Asian Pacific J Cancer Prevention, 2007, 8(2):253-7.
62. Christine Weyna, Selma Boulenouara, Vanessa Mathysb, Julie Vanhoolandta, Aurore Bernisa, Véronique Fontainea,* and the RIIP and INCTR Workshop Study Groupc. The “RIIP and INCTR Workshop Study Group” is composed of the following institutions and investigators: Pasteur Institute of French Guiana, Laboratory of Virus-Host Interactions: Dr. Vincent Lacoste, Pasteur Institute of Madagascar, Laboratory of Pathology: Dr. Clairette Raharisolo Vololonantenaina, Stephan Angeloff Institute of Microbiology, Department of Virology, Bulgaria : Dr. Angel S. Galabov and Peter Grozdanov, Cancer Institute (WIA), Department of Molecular Oncology, Chennai, India: Dr. Tithi Parija and Dr. Thangarajan Rajkumar, National Institute of Hygiene and Epidemiology, Hanoï, Vietnam: Dr. Nguyen Thi Thuong, Pasteur Institute of Tunisia, Laboratory of Pathology: Dr. Haifa Tounsi-Guettiti, Dr. Samir Boubaker and Dr. Emna Jerbi, Pasteur Institute of Cambodia, Laboratory of Pathology : Dr. Didier Monchy, Cantacuzino Institute, unit HPV, Bucharest, Romania : Dr. Niculina Coman, Tata Memorial Hospital, Department Microbiology: Preethi Vijayan, Pasteur Institute of Morocco, Laboratory of Molecular Biology : Dr. Abdelouaheb Bennani, Pasteur Institute of Ivorian Coast, Sexually transmitted Diseases Laboratory: Dr. Hortense Faye-Ketté and Dr. Mireille Dosso. Detection of human papillomavirus types 45 and 51 by type-specific polymerase chain reaction. J Virol Methods, 2007, 146: 405-08.
63. International Collaboration of Epidemiological Studies of Cervical Cancer. Analysis and writing committee: Paul Appleby, Valerie Beral, Didier Colin, Amy Berrington de González, Silvia Franceschi, Jane Green, Julian Peto, Martyn Plummer, Siân Sweetland. Steering committee: Carlo La Vecchia (Chairman), Xavier Bosch, Rolando Herrero, Allan Hildesheim, David Skegg, David Thomas. Collaborators: Cancer Epidemiology Research Group, National Health Laboratory Service, Johannesburg, South Africa: L Stein, MI Urban. Cancer Institute (WIA), Chennai, India: T Rajkumar. Cancer Research UK Epidemiology Group, Wolfson Institute of Preventive Medicine, UK: J Cuzick. Cancer Research UK Epidemiology Unit, Oxford, UK: P Appleby, R Barnabas, V Beral, A Berrington de González, D Bull, K Canfell, J Green, G Reeves, S Sweetland. Danish Cancer Society, Denmark: S Kjaer. Department of Public Health, Oxford, UK: R Painter, M Vessey. Fred Hutchinson Cancer Research Center, Seattle, USA: J Daling, M Madeleine, R Ray, D Thomas. Guanacaste Epidemiological Project, Costa Rica: R Herrero. Department of Medical Epidemiology and Biostatistics, Karolinska Institut, Sweden: N Ylitalo. Institut Català d’Oncologia: FX Bosch, X Castellsagué. Institut Nacional de Santé Publique, Algiers, Algeria: D Hammouda. Institute of Cancer Research, Sutton, UK, and London School of Hygiene and Tropical Medicine, London, UK: J Peto. Instituto Nacional de Enfermedades Neopláscias ‘Dr Eduardo Caceres Grazini’, Lima, Peru: C Santos. International Agency for Research on Cancer, Lyon, France: D Colin, S Franceschi, N Muñoz, M Plummer. Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy: C La Vecchia, E Negri. Lund University, Mälmo, Sweden: J Dillner, I Silins. Ministere de la Sante Publique et d’Affaires Sociales, Bamako, Mali: S Bayo. Ministry of Health, Morocco: N Chaouki. Ministry of Health, Paraguay: P Rolon. National Cancer Institute, NIH, USA: L Brinton, A Hildesheim, J Lacey Jr, M Schiffman. Royal College of General Practitioners Oral Contraception Study, UK: P Hannaford. Prince of Songkla University, Songkla, Thailand: S Chichareon. The Cancer Council New South Wales, Sydney Australia: F Sitas. Universidade de São Paulo, Brazil: J Eluf-Neto. University of Milan, Italy: C La Vecchia. University of Otago, New Zealand: D Skegg. University of Southern California, USA: M Pike, G Ursin. University of the Philippines, Manila, The Philippines: C Ngelangel. University of Tromsø, Norway: I T Gram. World Health Organisation, Geneva: T Farley. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data on 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet, 2007, 370(9599): 1609-1621.
64. Vijayalakshmi N, Selvaluxmi G, Majhi U and Rajkumar T*. Alterations found in p16/RB/Cyclin D1 pathway in the dysplastic and malignant cervical epithelium. Oncology Research, 2007, 16(11), 527-533.
65. Rajkumar T* and Yamuna M. Multiple pathways are involved in drug resistance to doxorubicin in an osteosarcoma cell line. Anti-Cancer Drugs, 2008, 19(3): 257-265 .
66. T.Rajkumar *, M.Samson, R.Rama, V.Sridevi, U.Mahji, R.Swaminathan, N.K.Nancy. TGFβ1 (LEU10PRO), p53 (ARG72PRO) can predict for increased risk for breast cancer in south indian women and TGFβ1 PRO (LEU10PRO) allele predicts response to neo-adjuvant chemo-radiotherapy. Breast Cancer Res and Treat. 2008, 112(1):81-87.
67. Sridevi V and Rajkumar T*. Genetics and Genomics of ovarian cancer. Chapter in Book titled “Ovarian Cancer - comprehensive and contemporary management", Jaypee Brothers,New Delhi, 2008, Editors: K Chitrathara, Shalini Rajaram, Amita Maheshwari.
68. Murhekar K, Majhi U, Sridevi V, Rajkumar T. Does "ichthyosis uteri" have malignant potential? : A case report of squamous cell carcinoma of endometrium associated with extensive ichthyosis uteri. Diagn Pathol. 2008 Jan 31;3(1):4
69. N Sudakar, Nirmala KA, Rajalekshmy KR, Rajkumar T. .Does TAL-1 Deletion Contribute to the High Incidence of T-Cell Acute Lymphoblastic Leukemia in South Indian Patients? Asian Pac J Cancer Prev. 2008 Jan-Mar;9(1):127-30.
70. Boyle P, Anderson BO, Andersson LC, Ariyaratne Y, Auleley GR, Barbacid M, Bartelink H, Baselga J, Behbehani K, Belardelli F, Berns A, Bishop J, Brawley O, Burns H, Clanton M, Cox B, Currow D, Dangou JM, de Valeriola D, Dinshaw K, Eggermont A, Fitzpatrick J, Forstmane M, Garaci E, Gavin AT, Kakizoe T, Kasler M, Keita N, Kerr D, Khayat D, Khleif S, Khuhaprema T, Knezevic T, Kubinova R, Mallath M, Martin-Moreno J, McCance D, McVie JG, Merriman A, Ngoma T, Nowacki M, Orgelbrand J, Park JG, Pierotti M, Ashton LP, Puska P, Escobar CV, Rajan B, Rajkumar T, Ringborg U, Robertson C, Rodger A, Roovali L, Santini LA, Sarhan M, Seffrin J, Semiglazov V, Shrestha BM, Soo KC, Stamenic V, Tamblyn C, Thomas R, Tuncer M, Tursz T, Vaitkiene R, Vallejos C, Veronesi U, Wojtyla A, Yach D, Yoo KY, Zatonski W, Zaridze D, Zeng YX, Zhao P, Zheng T. Need for global action for cancer control. Ann Oncol. 2008 Sep;19(9):1519-21.
71. Sasikala P S, Nirmala K, Shirley S, Majhi U, Rajkumar T (2008) Frequency and

distribution of EBV infection and its association with P53 expression in a series of

primary nodal NHL patients from South India. International J of Laboratory

Hematology. Epub Dec 4, 2008.

72. Suneetha KJ, Nirmala Nancy K, Rajalekshmy KR, Sagar TG, Rajkumar T. Role of GSTM1 and GSTP1 (Ile105Val) polymorphisms in susceptibility to acute lymphoblastic leukaemia among south Indian population. Asian Pacific J Cancer Prev, 2008, 9, 1-4.
73. N. Soumittra, V. Sridevi, S. Shirley, R.Narayanan, U. Majhi, T. Rajkumar*. A novel de-novo germline mutation in p53 in a patient with multiple early onset cancers. (submitted to Indian Journal of Cancer).

Details of Oncologic Experience

a) Professional / Practical Training:

A Special Trainee in the Dept. of Cancer Chemotherapy, Govt. Royapettah Hospital, from 16-7-95 to 15-1-96, under Prof. V.Srinivasan.

A Post-Graduate in D.M. (Medical Oncology) from April 1986 - March 1988. On successful completion of the course in March 1988, continued to work as a full-time faculty member in the Department of Medical Oncology, Cancer Institute, Adyar, Madras, India.

1. During this period, participated in treating patients with leukaemia and lymphomas, with intensive multidrug protocols (collaborative protocol with NCI., Paediatric branch).

2. Formulated a chemotherapeutic protocol for carcinoma of ovary, which is under trial.

3. Have done more than 25 intraperitoneal chemotherapy with Melphalan in the management of carcinoma ovary and malignant ascites.

4. Participated actively in the formulation of protocols for small cell lung cancer, soft-tissue sarcomas and high grade spindle cell sarcomas of bone (e.g. osteosarcoma). High grade spindle cell sarcomas of the bone are treated with the view to limb conservation. The trial is ongoing.

5. Participant of the team which did four autologous bone marrow rescue after high dose Melphalan.

6. Was the Medical Oncologist in charge of the management of Adult solid tumours.

b. Research Experience:

1. Laboratory

A. Worked on two short-term projects during my MBBS course.

i). Nosocomial Infection in Government General Hospital, Madras.

ii). Carrier status for parasitic infestation and typhoid bacilli, in food handlers in the city hotels.

B. Worked in the ICRF Molecular Oncology Unit, Hammersmith Hospital for my Ph.D.between 0ctober 1991and October 1994. The title of my thesis was "Analysis of the Expression and Function of the c-erbB3 protein in human tumours and Exploitation of its Targeting potential in Immunotherapy ".

RESEARCH PROGRAMS AND PROJECTS

* Established a Molecular Oncology Laboratory at the Cancer Institute. Recognised as a Guide for Ph.D. students by the M.G.R. Medical University, Anna University and Madras University. Two of the students has completed their Ph.D. and has been awarded their Ph.D (Their thesis were "Highly Commended"). Four students are currently registered for their Ph.D.
* PCR based detection of Minimal residual disease in Acute lymphoblastic leukemias. This study was funded by the NCI, Bethesda, USA. - completed.
* Study of type 1 tyrosine kinase growth factor receptors and their growth factors in breast and cervical cancers has been completed. The receptors studied include EGFR, c-erbB2 and the growth factors include Amphiregulin, Cripto, and Heregulin.
* BCL-2 and p53 expression in cervical cancers - completed.
* Biologic characterisation of T-ALL-Funding obtained from NCI, Bethesda, USA.-Completed
* Cell cycle regulatory molecules in cervical cancer - funding obtained from Dept. of Science and Technology, Govt. of India - Completed
* HPV in cervical cancer - a case control study - completed a collaborative programme with IARC, Lyon, France.

Publications arising from the study:

1. Rajkumar T, Franceschi S, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. The role of paan chewing and dietary habits in cervical carcinoma in Chennai, India. Br J Cancer, 88: 1388-1393, 2003.

2. Franceschi S, Rajkumar T, Vaccarella S, Gajalakshmi V, Sharmila A, Snijders PFJ, Munoz N, Meijer CJL, Herrero R. Human papilloma virus and risk factors for cervical cancer in Chennai, India: A case control study. Int. J Cancer, 107: 127-133, 2003.

* HPV in Oral Cancer-Funded by IARC, Lyon, France-Completed

Publications arising from the study:

1. Herrero R, Castellsague X, Pawlita M, Lissowska J, Kee F, Balaram P, Rajkumar T, Sridhar H, Rose B, Pintos J, Fernandez L, Idris A, Martinez C, Nieto A, Talamini R, Tavani A, Bosch FX, Snijders PJF, Viscidi R, Munoz N, Franceschi S. The viral etiology of oral cancer: evidence from the IARC multicentric study. JNCI. 95:1772-1783, 2003.
2. Rajkumar T, Sridhar H, Balaram P, Vaccarella S, Gajalakshmi V, Nanadakumar A, Ramdas K, Munoz N, Herrero R, Franceschi S and Weiderpass E. Oral cancer in Southern India: The influence of body size, diet, infections and sexual practices. Eur. J. Cancer Prevention, 12, 135-143, 2003.
3. Balaram P, Sridhar H, Rajkumar T, Vaccarella S, Herrero R, Nanadakumar A, Gajalakshmi V, Ravichandran K, Ramdas K, Sankaranaray anan R, Munoz N, Franceschi S. Oral cancer in Southern India: the influence of smoking, drinking, paan-chewing and oral hygiene. Int J Cancer, 98, 440-445, 2002.

* Identification of genes involved in radio-responsiveness in cervical cancer using differential display.-Funding obtained from DAE-Completed.

Gene expression before and after treatment (10 Gy) was studied in SiHa, a cervical carcinoma derived cell line. Differential display performed on non-irradiated and irradiated cells (10 Gy) using a combination of 3 anchor primers and 16 arbitrary primers yielded 20 differentially expressed fragments. Differential expression of one of the fragments differentially expressed in the irradiated sample was also confirmed in Northern blots. Cloning and sequencing of the fragment revealed it to be similar to a splice variant of the MRPS28 gene. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed using primers designed to amplify the splice variant and confirm the expression. In conclusion, this study shows that the splice variant kDec03 of the MRPS28 gene is differentially expressed in response to radiation in SiHa cells.

* Identification of genes involved in drug resistance in osteosarcomas using differential display and microarray

Osteosarcomas are highly malignant bone tumors predominantly seen in pediatric age group and young adults. The crude incidence rate of osteosarcoma has been found to be 0.8/100,000 population (males) and 0.6/100,000 population (females) (Madras Metropolitan Tumor Registry). The etiology of osteosarcoma is not known. Even though, the intensive chemotherapeutic regimens has increased the cure rates to 60-70%, failure still occur due to the spread of the disease, outside of the site of origin, most commonly to lungs. Drug resistance is of major concern in the management of osteosarcoma. To further enhance osteosarcoma therapy, it would be very important to identify newer prognostic markers and also, to develop new therapeutic strategies based on most effective combination of cytotoxic drugs.

The 143B osteosarcoma cell line have been selected for resistance to adriamycin, cisplatin and ifosfamide by intermittent exposure to stepwise increasing concentration of the drug. Three drug resistant osteosarcoma 143B cell lines to cisplatin, adriamycin and ifosfamide have been established. The folds of resistance generated have been determined by the difference in percentage of viable cells between wild type and drug resistant cells through Micro culture Tetrazolium Test. The differential expressed genes between wild type and drug resistant 143B cells were identified using differential display.

Differential display was done for ifosfamide resistant vs wild type 143B osteosarcoma cell line and cisplatin resistant vs wild type 143B osteosarcoma cell line, using 3 anchored primers and 16 arbitrary primers. 17 fragments were found to be differentially expressed among the amplified cDNA populations between wild type and ifosfamide resistant cell line, using anchored primer HT11A and HT11G. 12 fragments were found to be differentially expressed among the amplified cDNA populations between wild type and cisplatin resistant cell line, using anchored primer HT11A. The differentially expressed genes were confirmed by northern blot. The differentially expressed genes will be sequenced and identified in BLAST homology search.

Microarray was used to do the gene expression profiling of the parental and the doxorubicin drug resistant cell lines. Of the 75 genes up or down regulated, 21 were taken up for further validation using Real time PCR. 11 genes were confirmed to have either up or downregulation – MDR1, KLF2, IL8 were some of the genes upregulated; p53, Topoisomerase IIb, ECOP etc. were downregulated in the drug resistant cell line. Several novel pathways were found to be involved in the induction of drug resistance. Work is on progress to target these pathways in order to reverse the drug resistance.

Publications

o Rajkumar T* and Yamuna M. Multiple pathways are involved in drug resistance to doxorubicin in an osteosarcoma cell line. Anti-Cancer Drugs

* Establishing a Population based Hereditary Cancer Registry covering Madras Metropolitan Area – funded by WHO between Jan 2002 to Dec 2003; thereafter by Cancer Institute (WIA)

The population based Hereditary cancer registry covers the Chennai Metropolitan area. Questionnaire based data collection and blood sample is collected for gene analysis after an informed consent. Till date, 275 families have been registered.
Total number of cases enrolled 275
Number of families with two members affected with cancer 179
Numbers of families with more than two members affected with cancer 64
Number of hereditary non-polyposis colo-rectal cancer families 5
Number of hereditary breast and ovarian cancer families 24
Number of hereditary ovarian cancer families 1
Number of early onset breast cancer cases 15
Number of early onset colo-rectal cancer cases 14
Number of early onset ovarian cancer cases 3

* Mutation analysis for hereditary breast cancers and hereditary colo-rectal cancers and their prognostic significance - Funded by Dept. of Biotechnology, Govt. of India – Now by Cancer Institute (WIA).

Hereditary breast and ovarian cancer study

A total of 80 cases have been analyzed for mutations in the BRCA1 and BRCA2 genes and for CHEK2 1100 del C. Eight pathogenic mutations have been identified in these cases. Four of these are novel and have been submitted to GenBank.

Many known polymorphisms were identified both in BRCA1 and BRCA2 genes in all except three cases. CHEK2 1100 del C was not seen in any of the cases so far analyzed.

The details are given below.

* No: of women with breast/ovarian cancer studied - 80
* No: of controls studied - 1
* No: of disease causing mutation detected - 12/80 (15%)
* No: of variants of unknown significance detected - 1/80 (1.2%)
* No: of samples wherein polymorphisms detected - 77/80 (96%)
* No: of samples with no polymorphisms in BRCA1 - 20/80 (25%)
* No: of samples with no polymorphisms in BRCA2 - 10/80 (12.5%)

Disease causing mutations in BRCA1 and BRCA2

S.No.

BRCA1

1 Exon 12 – c.4158_4162delCTCTC; p.Ser1369Ser fsX2
2 Exon 13 – c.4327C>T; p.R1443X
3 Exon11C – c.1148_1149delAT; p.Asn383Arg fsX6
4 Exon17 – c.5024_5025insT; p. Thr1675Thr fsX4
5-8 Exon2 – c.68_69delAG; p. Glu23Val fsX16 in totally 4 cases
9 Exon14 – c.4399C>T; p.Gln1467X
10 Exon 16 - c.4705_4706insTGGAATC; p.Ile1567fsx5

BRCA2

11 Exon 11O – c.6214_6218delCTTAA; p.Ser2072Ser fsX4
12 Exon 11D – c.5130_5133delTGTA; p.Tyr1693X

Hereditary colo-rectal cancer study.

Under this study a total of 76 cases have been analysed. First screen was done by microsatellite instability analysis (MSI), followed by mutational screen of hMLH1 and hMSH2 gene.

Ten mutations have been identified and four of them are novel. Few polymorphisms were also identified.

The details are given below.

No. of cases that showed disease causing mutation – 5/76 (6.6%)

No. of cases that showed mutation of unknown significance – 5/76 (6.6%)

Mutations in hMLH1 and hMSH2
S No. hMLH1
1 Splice site –intron 16- c.1897- 2A>G
2 Exon18 – c.2011G>T; p.Glu671X
3 Exon18 –c.2038T>G; p. C680G
4 Exon 10 - c.793C>A;pR265S
hMSH2
5 Exon 13 –c.2038C>T; p.R680X
6 Exon 3 - c.387_388delTC; p. Ser129Ser fsX2
7 Exon 15 - c.2632_2633delAG; p.Glu878Ala fsX2
8 Exon 3 - c.513G>A; pR171K
9 Exon 1 - c.67T>C; p.F23L
10 Exon 13 - c.2205C>T; p.I735

Few polymorphisms were also identified. The novel mutations have been submitted to the GenBank.

The above studies are funded by the DBT initially and now by the Cancer Institute (WIA).

Publications:

1. Rajkumar T*, Soumittra N, Nirmala Nancy, Swaminathan R, Sridevi V, Shanta V BRCA1, BRCA2 and CHEK2 (1100 del C) germline mutations in hereditary breast and ovarian cancer families in South India. Asian Pac J Cancer Prevent. 4: 203-208, 2003.
2. Rajkumar T*, Soumittra N, Durgatosh Pandey, Karunakaran Nirmala Nancy, Vikas Mahajan and Urmila Majhi. Mutation analysis of hMSH2 and hMLH1 in colo-rectal cancer patients in India. Genetic Testing, 8:157-162, 2004.
3. Rajkumar T, Soumittra N, Vidubala E, Sridevi V, Mahajan V, Ramanan SG, Vijaya S. Organization and running of the first comprehensive hereditary cancer clinic in India. Hereditary Cancer in Clinical Practice 3(4) pp. 165-170, 2005.

* Development and clinical evaluation of dendritic cell vaccine for HPV related cervix cancer - Funded by Dept. of Biotechnology, Govt. of India

In the case of cervical cancer patients with HPV infection, the Immune system seems to play a significant role. The presence of high risk HPV alone is not sufficient though critical. The dysfunction is due to loss of effective presentation of antigenic peptide to the Immune cells and aberrations in effector systems. Dendritic cells are potent Antigen Presenting Cells, hence this property can be exploited to increase the population of both specific CD4 and CD8 T cells.

The immature dendritic cells were developed by growing peripheral blood monocytes in the presence of IL4 and GM-CSF for 7days. These were found to be HLA-DP, DQ, DR ++; CD86+ and CD14 –ve.

On further incubation of the immature Dendritic cells in the presence of TNF-a and IL 1 b for 3days, they achieved the mature phenotype – HLA DP, DQ, DR +++; CD86++; CD14 –ve.

The immature dendritic cells were primed with tumour cell lysate or tumour RNA The Dendritic cells were then grown in the presence of TNF –a and IL 1 b for 3days, before processing for FACS and for functional studies.

The functional studies indicated that priming can make the dendritic cells (which are irradiated prior to use) efficient in presenting the antigens to allogenic lymphocytes. Tumour lysates were found to induce a strong response in the allogenic lymphocytes, when used at 3:1 ratio.

Cervical cancer patients with recurrent disease, for whom no further standard line of treatment is available, were included in the study. The patients were randomized into three arms: 1) Saline only 2)unprimed mature Dendritic cells 3)Mature Dendritic cells primed with tumor lysate. The phase 1 study has accrued 10 patients so far. No toxicity has been noted except for low grade fever, pain at the site of injection, mild vomiting etc. No objective tumour response was seen. Two patients demonstrated DTH response and two of three arm III patients and one of four Arm II patient were positive for the intracellular CD3-IFNγ assay. An additional five patients will be recruited into the study before proceeding with the Phase 2 study.

* Genetic polymorphisms and breast cancer – Funded by Chennai Willingdon Corporate Foundation

The objective of the project is to do a Case-Control study (250 Breast Cancer Cases and 500 Controls) for evaluating the allelic frequencies of the polymorphisms in TGFβ Leu 10 Pro), c-erbB2 (Ile655Val), p53 (Arg72Pro), CYP17 (T-34C), CYP19 (Trp39Arg),, GSTP1 (Ile462Val), GSTM1 (Present/Null) genes, and to assess the association of the polymorphism with breast cancer incidence.

So far, 250 breast cancer cases and 500 controls have been enrolled in the study. Analysis has been completed for all the genes listed above. Additional genes are being included for study.

Publications:

o M.Samson, R.Swaminathan, R.Rama, V.Sridevi, K.Nirmala Nancy, T.Rajkumar*. Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and p53 (Arg72Pro) genetic polymorphisms and the risk of breast cancer – A case control study from South India. Asian Pacific J Cancer Prevention, 2007, 8(2):253-7.
o T.Rajkumar *, M.Samson, R.Rama, V.Sridevi, U.Mahji, R.Swaminathan, N.K.Nancy. TGFβ1 (LEU10PRO), p53 (ARG72PRO) can predict for increased risk for breast cancer in south indian women and TGFβ1 PRO (LEU10PRO) allele predicts response to neo-adjuvant chemo-radiotherapy. Breast Cancer Res and Treat. (Accepted, 2007).

Minimal Residual Disease detection in cervical cancer – Indo-German collaborative project – ICMR funded.

The study will use APOT (Amplication of Papilloma virus Oncogene Transcripts) for the detection and follow-up of patients treated for cervical cancer. A second component of our study will try to develop an ELISA based assay for detection of p16 in the plasma of patients with cervical cancer and use them for follow-up of patients. The ELISA assay will be developed by Prof. Knebel’s group and then used in our laboratory.

107 cervical cancer cases and 200 controls have been recruited for the study. Follow up samples have been collected from all the patients, with some completing more than 6 follow-up visits. APOT assay has been done in 70 cases, of which HPV-16 was 53 and HPV-18, 17 in number.

* APOT Assay and Sequencing : 70 samples have been sequenced of which

HPV 16 53 HPV 18 17

Integrated 32 Integrated 13

Episomal 21 Episomal 2

Both (Int & Epi) 2

The study has shown a high incidence of Episomal state of HPV16 in the invasive cancers (21/53) (40%), in the South Indian patients.

Gene expression studies in cervical, breast and gastric cancers

Under support from DST for the establishment of the Centre of Excellence for Molecular Oncology in 2007, projects to study the gene expression patterns in cervical, breast and gastric cancer. The study will help identify prognostic markers for these cancers and help in developing assays for prognostication in these cancers using low-density microarray or using Real time PCR.

This program has just been started.

Development of structure based drugs against EWS:FLI fusion protein seen in Ewing’s sarcoma.

This project has just commenced under support from DST for the establishment of the Centre of Excellence for Molecular Oncology in 2007.
CLINICAL PROGRAMS

* Running the country's first comprehensive Hereditary cancer clinic at the Institute.
* Evaluation of the Dendritic vaccine for the treatment of cervical cancer - DBT funded study.

MEMBER

* Programme Advisory Committee, Dept. of Science and Technology
* Task Force on Multi centre National programme on cervical cancer, Dept. of Biotechnology, Govt. of India.
* Member, Thematic Review Committee for Health Informatics, CDAC, Dept. of Information and Technology, Govt. of India.
* Member Secretary, Scientific Advisory committee of Cancer Institute (WIA).
* Member, Scientific Advisory committee of Vision Research Foundation, Sankara Nethralaya, Chennai.
* Member Secretary, Ethical committee of Cancer Institute (WIA).
* Member, Ethical committee of YRG AIDS Research Foundation.
* Treasurer, Asia and Pacific Federation of Organizations for Cancer Control, treatment and research (APFOCC).
* Chairman, Membership Committee, Asia Oceania Organizations (for research on) Gynaecological Infections and Neoplasia (AOGIN).
* Member, Editorial Board, Hereditary Cancer in Clinical Practice.
* Member, Editorial Board, Indian Journal of Cancer

REVIEWER
PROJECTS

# Dept. of Science and Technology, Govt. of India
# Dept. of Biotechnology, Govt. of India
# Indian Council of Medical Research, Govt. of India
# Welcome Trust, UK

JOURNALS

# British Journal of Cancer
# Asia Pacific Journal of Cancer Prevention
# Indian Journal of Biochemistry and Biophysics
# Indian Journal of Medical and Paediatric Oncology

FELLOWSHIP and MEMBERSHIP

o Fellow of the National Academy of Medical Sciences (FAMS)
o Indian Society of Oncology
o Indian Association of Cancer Research
o Indian Society of Human Genetics
o Indian Society of Medical and Paediatric Oncology
o Asia Pacific Organisation for Cancer Prevention

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