Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma.

Abstract:

:In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for comparison of the molecular profiles of eight grade III and four grade I stage III serous papillary adenocarcinomas. With a modified F-test in conjunction with random permutations, 99 genes whose expression was significantly different between grade I and grade III tumors were identified (P < 0.01). A disproportionate number of these differentially expressed genes were located on the chromosomal regions 20q13 and all exhibited higher expression in grade III tumors. Interphase fluorescent in situ hybridization demonstrated 20q13 amplification in two of the four grade III and none of the three grade I tumors available for evaluation. Several centrosome-related genes also showed higher expression in grade III tumors. We propose a model in which tumor differentiation is inversely correlated with the overexpression of several oncogenes located on 20q13, a common amplicon in ovarian and numerous other cancers. Dysregulation of centrosome function is one potential mechanistic link between genetic/epigenetic changes and the poorly differentiated phenotype in ovarian cancer.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Jazaeri AA,Lu K,Schmandt R,Harris CP,Rao PH,Sotiriou C,Chandramouli GV,Gershenson DM,Liu ET

doi

10.1002/mc.10098

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

53-9

issue

2

eissn

0899-1987

issn

1098-2744

journal_volume

36

pub_type

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