Chromosomal alterations in 98 endometrioid adenocarcinomas analyzed with comparative genomic hybridization

Abstract

The aim of the present study was to investigate chromosomal alterations in a large set of homogeneous tumors, 98 endometrioid adenocarcinomas. We also wanted to evaluate differences in chromosomal alterations in the different groups of tumors in relation to stage, survival and invasive or metastatic properties of the tumors. Comparative genomic hybridization (CGH) was used to detect chromosomal alterations in tissue samples from 98 endometrioid adenocarcinomas. All chromosomes were involved in DNA copy number variations at least once in the tumor material, but certain changes were recurrent and rather specific. Among the specific changes, it was possible to identify 39 chromosomal regions displaying frequent DNA copy number alterations. The most frequent alteration was detected at 1q25→q42, in which gains were found in 30 cases (30%). Gains at 19pter→p13.1 were detected in 26 tumors (26%) and at 19q13.1→q13.3 in 19 tumors (19%). Increased copy numbers were also detected at 8q (8q21→q22 and 8q22→qter), at a relatively high rate, in 17 cases (17%). Furthermore, gains at 10q21→q23 and 10p were found in 14 (14%) and 13 cases (13%), respectively. The most common losses were found in the three regions 4q22→qter, 16q21→qter and 18q21→qter, all of which were detected in eight of the 98 tumors (8%). We also detected differences between the tumors from deceased patients and from survivors. Gain at 1q25→q42 was more commonly detected in the tumors from patients who died of cancer. We noted that the regions most affected differed in the different surgical stages (I–IV). The results of the CGH analysis identify specific chromosomal regions affected by copy number changes, appropriate objects for further genetic studies.

Genomic Characterization of Gene Copy-Number Aberrations in Endometrial Carcinoma Cell Lines Derived from Endometrioid-Type Endometrial Adenocarcinoma

“…Therefore, the five cell lines studied rep-resent good model systems for studying EC signaling pathways and, perhaps, therapeutics in vitro and in preclinical animal model experiments. To support this notion, the consistent gains or losses we identified (gains in 2q, 3q, 3p, 5q, 17q, 7p, and 19q and losses in 3p,10p, 10q, 11q, 11p, 14q, 15q, 18p, and 21q) are consistent with those reported for EC patients (4, 5). …”

“…Chromosomal abnormalities, including DNA copy–number gains and/or losses are hallmarks of cancers (3). In a comparative genomic hybridization (CGH) study of 98 cases of EC, Levan et al ., (4) reported frequent amplifications in the chromosomal regions 1q25-42, 19pter-p13.1, 19q13.1-q13.3, 8q21-22, 10q21-q23, and 10p, and frequent losses in the regions 4q22-qter, 16q21-qter, and 18q21-1ter. Another CGH analysis of 43 human primary ECs revealed gains at 1q25-q41, 8q11.1-q21.1, and 8q21.3-qter, whereas the most frequently detected loss was at 16q11.2-q22 (5).…”

Genome-wide single-nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in the PI3-kinase pathway

“…LOH was detected on 1p (19%), 1q (10%), 2q (13%), 5q (13%), 6q (19%), 9p (16%), 9q (16%), 10q (29%), 16q (19%), 17p (16%) and 22p (10%) (Figure 1 and Supplementary Table 2). The regions of these gains and losses were compatible with the reports by comparative genomic hybridization (CGH) (Suehiro et al, 2000;Micci et al, 2004;Levan et al, 2006). CNN LOH involves allelic changes, including hemizygous deletion with a gain of the opposite allele.…”

“…The ratio of LOH in PTEN has been reported to be 20-40% by microsatellite markers and approximately 15% by CGH (Sirchia et al, 2000;Suehiro et al, 2000;Toda et al, 2001;Micci et al, 2004;Levan et al, 2006). In our analysis, four of seven LOH detected at the PTEN locus turned out to be CNN LOH, indicating that LOH of PTEN has been underestimated by CGH in endometrial carcinomas.…”

Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation

“…We found 11 significantly amplified and 13 significantly deleted regions of the genome (Table S4), including several that had been noted previously (8,9). For each we selected the peak region (ie, the highest frequency and amplitude of events) as the region most likely to contain a cancer gene target.…”