Detection of DNA gains and losses in primary endometrial carcinomas by comparative genomic hybridization

Abstract

Comparative genomic hybridization (CGH) was used in a retrospective analysis of chromosomal imbalances in frozen primary tumor specimens from 14 endometrial carcinoma patients. Chromosome changes were detected in nine cases (64%), and tumor stage and grade tended to parallel the degree of genomic imbalances. Gain of the entire long arm of chromosome I was observed in six cases (43%), three of which displayed only this chromosome change. Other common sites of copy number increases included 8q21 → qter (4 cases), 10p15 (4 cases), 10q11 → q24 (3 cases), and 13q21 → qter (3 cases, each with stage III disease). Two of the tumors with gains of chromosome 10 involved the whole chromosome, and this was the sole abnormality in one case. DNA amplification at 5p14 → p15 was identified in one specimen, a stage III tumor having numerous imbalances. DNA microsatellite analysis revealed multiple replication errors (RER), indicative of the RER+ phenotype, in four of 13 (31%) cases evaluated. The RER+ phenotype was observed in four of six stage Ia tumors but in none of seven stage Ib or stage III tumors. Multiple genomic imbalances detected by CGH were not observed in RER+ tumors but were detected in five of nine tumors without the RER+ phenotype. These investigations demonstrate the feasibility of CGH for the retrospective assessment of chromosomal changes in endometrial carcinoma specimens. Moreover, these data suggest that the etiologies in tumors with and without the RER+ phenotype may differ. Genes Chromosom. Cancer 18:115–125, 1997. © 1997 Wiley‐Liss, Inc.

Creation of tumorigenic human endometrial epithelial cells with intact chromosomes by introducing defined genetic elements

“…Similar findings have been obtained in studies of human embryonic kidney epithelial cells (Zimonjic et al, 2001). Recent comparative genomic hybridization analyses have revealed that fewer chromosomes exhibit genomic alterations in endometrial cancer than in other types of tumors (Sonoda et al, 1997). Such genomic imbalances are rarely observed in endometrial cancers, especially those with defective MMR (Hirasawa et al, 2003); this is consistent with the present results.…”

An Oncogenic Role for the Phosphorylated h-Subunit of Human Translation Initiation Factor eIF3

“…The gene encoding eIF3h is located in the long arm of chromosome 8 (specifically, 8q23-24), a region that is frequently amplified in many tumor types (22)(23)(24). For example, gain at 8q has been detected in bladder (25), endometrial (26), ovarian (27), and hepatocellular tumors (28). Although other genes, such as MYC and TRPSI, are also associated with the 8q23-24 region, only the EIF3h gene is consistently overexpressed in breast, prostate, and hepatocellular cancers (11)(12)(13)(14)(15).…”

Genetic Imbalances in Precursor Lesions of Endometrial Cancer Detected by Comparative Genomic Hybridization

“…So far, CGH analysis of 47 endometrioid adenocarcinomas of the endometrium has been reported. 18,28,29 Aberrant CGH profiles were found in 27 carcinomas, mainly comprising cases without MI. 1q and 8q overrepresentations were found to be the most consistent alterations, occurring in 20 out of 27 (74%) and 8 out of 27 (62%) of abnormal cases, respectively.…”