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
1.
Koul S, Houldsworth J, Mansukhani
M, Donadio A, McKiernan JM, Reuter VE,
Bosl GJ, Chaganti RSK, Murty VVVS.
Characteristic promoter mypermethylation
signatures in male germ cell tumors.
Molecular Cancer 1: 8, 2002.
2.
Narayan G, Pulido HA, Koul
S, Liu X-Y, Harris CP, Yeh YA,
Vargas H, Posso H, Terry MB,
Gissmann L, Schneider
A, Mansukhani M, Rao
PH, Murty VVVS. Genetic Deletions
Affecting Chromosome 2q34-q35 and
2q36.3-q37.1 Identify Sites of Putative
Tumor Suppressor Genes Involved in
Cervical Cancer Progression.
Oncogene 22: 3489-3499, 2003.
3.
Narayan G, Arias-Pulido H , Koul
S, Vargas H, Zhang FF , Villella J,
Schneider A, Terry MB, Mansukhani M,
Murty VV. Frequent promoter methylation
of CDH1, DAPK, RARB, and HIC1 genes in
carcinoma of cervix uteri: Its
relationship to clinical outcome.
Molecular Cancer 2: 24, 2003.
4.
Rao PH, Arias-Pulido H, Lu XY,
Harris CP, Vargas H, Zhang FF, Narayan
G, Schneider A, Terry MB, Murty VVVS.
Chromosomal amplifications, 3q gain and
deletions of 2q33-q37 are the frequent
genetic changes in cervical carcinoma.
BMC Cancer
2004, 4:5.
5.
Michel L, Diaz-Rodriguez E,
Narayan G, Murty VVVS, Benezra R.
Complete loss of the tumor suppressor
MAD2 causes premature cyclin B
degradation and mitotic failure in human
somatic cells. Proc Natl Acad Sci,
USA 101: 4459-4464, 2004.
6.
Narayan G, Arias-Pulido H,
Nandula SV, Basso K, Sugirtharaj DD,
Vargas H, Mansukhani M, Villella J,
Meyer L, Schneider A, Gissmann L,
Dürst M,
Pothuri B, Murty VVVS: Promoter
Hypermethylation of FANCF:
Disruption of Fanconi Anemia-BRCA
Pathway in Cervical Cancer. Cancer
Res 64: 2994-2997, 2004.
7.
Koul S, McKiernan JM,
Narayan G, Houldsworth J, Bacik J,
Dobrzynski DL, Assaad AM, Mansukhani M,
Reuter VE, Bosl GJ, Chaganti RS, Murty
VV. Role of promoter hypermethylation in
Cisplatin treatment response of male
germ cell tumors. Molecular Cancer
2004, 3:16, 2004.
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