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.

Selected Publications:

• Fakruddin, J. M., Chaganti, R.S.K., and Murty, V.V.V.S.: Lack of BCL10 mutations in germ cell tumors and B-Cell lymphoma. Cell 97: 683-684, 1999.

• Murty, V.V.V.S., Montgomery, K., Dutta, S., Bala, S., Renault, B., Bosl, G.J., Kucherlapati, R., and Chaganti, R.S.K.: A 3-Mb high-resolution BAC, PAC contig of 12q22 encompassing the 830 kb consensus minimal deletion in male germ cell tumors. Genome Res. 9: 662-671, 1999.

• Bala, S., Oliver, H., Renault, B., Montgomery, K., Dutta, S., Rao, P.H., Houldsworth, J., Kucherlapati, R., Wang, X., Chagatni, R.S.K., and Murty, V.V.V.S.: Genetic analysis of the APAF1 gene in male germ cell tumors. Genes, Chromosomes & Cancer 28: 258-268, 2000.

• Yeh, Y.A., Rao, P.H., Cigna, C., Middlesworth, W., Lefkowitch, J.H., and Murty, V.V.V.S.: Trisomy 1q, 2 and 20 in a case of hepatoblastoma: Possible significance of 2q35-q37 and 1q12-q21 rearrangements. Cancer Genetics and Cytogetics 123: 140-143, 2000.

• Pulido H.A., Fakruddin, M.J., Chatterjee, A., Esplin, E.D.,Beleño, N., Martínez, G., Posso, H., Evan, G.A, Murty, V.V.V.S.: Identification of a 6 cM Minimal Deletion at 11q23.1-23.2 and Exclusion of PPP2R1B Gene as a Deletion Target in Cervical Cancer. Cancer Res. 60: 6677-6682, 2000.

• Michel, L.S., Liberal, V., Chatterjee, A., Kirchwegger, G., Pasche, B., Gerald. W., Dobles, M., Sorger, P.K, Murty, V.V.V.S., and Benezra, R.: MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells. Nature 409: 355-359, 2001.

• Montgomery, K.T., Lee, E. , Miller, A., Lau, S., Shim, C., Decker, J., Chiu, D., Emerling, S., Sekhon, M., Rachel Kim, R., Lenz, J., Han, J., Ioshikhes, I., Renault, B., Marondel, I., Yoon, S-J.K, Song, K., Murty, V.V.V.S., Scherer, S., Yonescu, R., Kirsch, I., Thomas Ried, T., McPherson, J., Gibbs, R., and Kucherlapati, R.: A high-resolution STS content map of human chromosome 12. Nature 409: 945-946, 2001.

• Chatterjee, A., Pulid0, H.A., Koul, S., Beleño, N., Perilla, A., Posso, H., Manusukhani, M., Murty, V.V.V.S.: Mapping the Sites of Putative Tumor Suppressor Genes at 6p25 and 6p21.3 in Cervical Carcinoma: Occurrence of Allelic Deletions in Precancerous Lesions. Cancer Res. 61: 2119-2123, 2001.