The efforts of this laboratory are directed toward the understanding genetic and epigenetic aspects of cervical cancer and hematologic malignancies. One of the major goals is to make attempts to identify prognostic markers of response to treatment.
Carcinoma of uterine cervix is a common malignancy among women worldwide. Most cervical cancers are preceded by distinct preneoplastic epithelial changes, which progress to invasive cancer, thus providing opportunities to study genetic alterations at an early stage of transformation. In a genome-wide search for genetic alterations, we have identified several sites of copy number alterations, gene amplifications, and specific genetic pathways in invasive cancer. We are currently evaluating a predictive biomarker of apoptotic response to stratify patients that benefit combination drug therapy.
In leukemia and lymphoma, a similar strategy is applied to identify genetic and epigenetic predictive markers of response to treatment. Preclinical validations of a number of epigenetically inactivated markers are underway.
1. Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Murty VV. Identification of Copy Number Gain and Overexpressed Genes on Chromosome Arm 20q by an Integrative Genomic Approach in Cervical Cancer: Potential Role in Progression. Genes Chromosomes and Cancer 47: 755-765, 2008.
2. Narayan G, Scotto L, Neelakantan V, Kottoor SH, Wong AH, Loke SL, Mansukhani M, Pothuri B, Wright JD, Kaufmann AM, Schneider A, Arias-Pulido H, Tao Q, Murty VV. Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer. Genes Chromosomes Cancer 48: 983-992, 2009.
3. Narayan G, Murty VV: Integrative genomic approaches in cervical cancer: Implications for molecular pathogenesis. Future Oncology. 6: 1643-1652, 2010.
4. Narayan G, Freddy AJ, Xie D, Liyanage H, Clark L, Kisselev S, Kang JU, Nandula SV, McGuinn C, Subramaniyam S, Alobeid B, Satwani P, Savage D, Bhagat G, Murty VV. Promoter Methylation-Mediated Inactivation of PCDH10 in Acute Lymphoblastic Leukemia Contributes to Chemotherapy Resistance. Genes, Chromosomes and Cancer 50: 1043-1053, 2011.
5. Gonda TA, Glick MP, Sethi A, Poneros JM, Palmas W, Iqbal S, Gonzalez S, Nandula SV, Emond JC, Brown RS, Murty VV, Stevens PD. Polysomy and p16 deletion by fluorescence in situ hybridization in the diagnosis of indeterminate biliary strictures. Gastrointest Endosc. 75: 74-79, 2012.
6. Debata PR, Castellanos MR, Fata JE, Baggett S, Rajupet S, Szerszen A, Begum S, Mata A, Murty VV, Opitz LM, Banerjee P, A Novel Curcumin-based Vaginal Cream Vacurin Selectively Eliminates Apposed Human Cervical Cancer Cells. Gynecol Oncol 29: 145-153, 2013.
7. Narayan G, Xie D, Freddy AJ, Ishdorj G, Satwani P, Liyanage H, Clark L, Kisselev S, Nandula SV, Scotto L, Alobeid B, Savage D, Tycko B, O’Connor OA, Bhagat G, Murty VV.. PCDH10 Promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis. Genes Chromosomes Cancer 52: 1030-1041, 2013.
8. Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, Wechsler J, Yang J, Hayes J, Klein RJ, Zhang J, Wei L, Wu G, Rusch M, Nagahawatte P, Ma J, Chen SC, Song G, Cheng J, Meyers P, Bhojwani D, Jhanwar S, Maslak P, Fleisher M, Littman J, Offit L, Rau-Murthy R, Fleischut MH, Corines M, Murali R, Gao X, Manschreck C, Kitzing T, Murty VV, Raimondi SC, Kuiper RP, Simons A, Schiffman JD, Onel K, Plon SE, Wheeler DA, Ritter D, Ziegler DS, Tucker K, Sutton R, Chenevix-Trench G, Li J, Huntsman DG, Hansford S, Senz J, Walsh T, Lee M, Hahn CN, Roberts KG, King MC, Lo SM, Levine RL, Viale A, Socci ND, Nathanson KL, Scott HS, Daly M, Lipkin SM, Lowe SW, Downing JR, Altshuler D, Sandlund JT, Horwitz MS, Mullighan CG, Offit K. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet. 45:1226-1231, 2013.