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Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma
Author(s) -
Jazaeri Amir A.,
Lu Karen,
Schmandt Rosemarie,
Harris Charles P.,
Rao Pulivarthi H.,
Sotiriou Christos,
Chandramouli G. V. R.,
Gershenson David M.,
Liu Edison T.
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10098
Subject(s) - biology , ovarian cancer , cancer research , serous fluid , ovarian carcinoma , fluorescence in situ hybridization , clear cell carcinoma , centrosome , comparative genomic hybridization , tissue microarray , phenotype , epigenetics , microarray , amplicon , cancer , gene , gene expression , genetics , cell cycle , chromosome , polymerase chain reaction , biochemistry
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. Published 2003 Wiley‐Liss, Inc.