Research Summary

The efforts of this laboratory are directed toward the understanding the genetic basis of cancer with specific goals to identify novel tumor suppressor genes (TSGs) and their mechanisms of tumor suppression in male germ cell tumor (GCT) and cervical cancer.

GCT, a common malignancy in young males, is a complex tumor system where germ cells undergo transformation and exhibit embryonal and extra-embryonal like differentiation patterns. In an extensive genetic analysis, we have identified critical regions of deletion at 12q13, 12q22 and 5p15.1-15.2 suggesting the presence of TSGs at these regions. Extensive physical and deletion maps, sequence annotation and transcript map of 12q22 region have been generated in a prelude to identify the gene. Currently, we are exploring the role of genetic and epigenetic mechanisms of tumor suppression related to 12q22 deletions in GCT.

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 deletions and gene amplifications in invasive cancer. We are currently mapping precancerous lesions through the spectrum of progression to identify genetic alterations and to develop genetic prognostic model for progression. Ultimate goals of these studies are to understand genetic mechanisms of cervical carcinogenesis.

Service Activities

Cytogenetic and molecular cytogenetic testing of hematologic and solid malignancies.
Department of Pathology, Columbia University Medical Center

Selected Publications

1. Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, Mansukhani M, Villella J, Meyer L, Schneider A, Gissmann L, Dorst M, Pothuri B, Murty VV: Promoter Hypermethylation of FANCF: Disruption of Fanconi Anemia-BRCA Pathway in Cervical Cancer. Cancer Res 64: 2994-2997, 2004.

2. Narayan G, Goparaju C, Arias-Pulido H, Kaufmann AM, Schneider A, Durst M, Mansukhani M, Pothuri B, Murty VV: Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Molecular Cancer 5:16, 2006.

3. Narayan G, Goparaju C, Arias-Pulido H, Kaufmann AM, Schneider A, Durst M, Mansukhani M, Pothuri B, Murty VV: Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Molecular Cancer 2006, 5:16.

4. Subramaniyam S, Nandula SV, Nichols G, Weiner M, Satwani P, Bachir Alobeid B, Bhagat G, Murty VV: Do RARA/PML Fusion Gene Deletions Confer Resistance to ATRA Based Therapy in Patients with Acute Promyelocytic Leukemia? Leukemia. 20:2193-2195, 2006.

5. Narayan G, Bourdon V, Chaganti S, Arias-Pulido H, Nandula SV, Rao PH, Gissmann L, Durst M, Schneider A, Pothuri B, Mansukhani M, Basso K, Chaganti RS, Murty VV: Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: Identification of candidate amplified and overexpressed genes. Genes Chromosomes Cancer 46: 373-384, 2007.

6. Zudaire E, Cuesta N, Murty VV, Woodson K, Adams L, Gonzalez N, Martonez A, Narayan G, Kirsch I, Franklin W, Hirsch F, Birrer M, Cuttitta F: The aryl hydrocarbon receptor repressor is a putative tumor suppressor gene in multiple human cancers. J Clin Invest. 118: 640-650, 2008.

7. 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.

8. Scotto L, Narayan G, Nandula SV, Subramaniyam S, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Schneider A, Arias-Pulido A, Murty VV: Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha. Molecular Cancer 7: 58, 2008.

Honors and Awards

1984-1985 World Health Organization Fellow, Memorial Sloan Kettering Cancer Center, New York.

Committees , Council, and Professional Society Memberships

Associate Editor, Molecular Cancer (A BioMed Central Journal)

Member, Clinical Advisory Board, CancerGenetics, Inc.

Keywords

Cancer Cytogenetics, Diagnosis, Fluorescence In Situ Hybridization (FISH), Spectral Karyotyping, Testicular Germ Cell Tumor, Cervical Cancer, Molecular Genetics

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