Relation of DNA ploidy to genetic aberrations detected by chromosomal CGH and FISH in gastric adenocarcinomas

Abstract

Abstract. We analyzed DNA copy number aberrations (DCNAs) by chromosomal comparative genomic hybridization (CGH) in 93 consecutive sporadic gastric adenocarcinomas. In addition, numerical aberrations in chromosomes 7, 11, 17, and 18 were evaluated by fluorescence in situ hybridization (FISH). Gastric cancers were divided on the basis of nuclear DNA content measured by laser scanning cytometry (LSC) into two groups, 36 DNA diploid (1.0 ≤ DNA index (DI) < 1.2) and 57 aneuploid (DI ≥ 1.2) cancers. The most frequent gain and loss of DNA copy number were found at 8q21-23 and 19p13.3, respectively, in both diploid and aneuploid cancers. Diploid cancers were further divided on the basis of genetic aberrations into major type and subtype cancers. The diploid cancer group included nine subtype cancers that showed large numbers of DCNAs; the mean number of DCNAs detected by CGH was 26.7 per tumor. This value was much larger in these diploid subtype cancers than diploid major type cancers (mean, 5.2 per tumor, p<0.0001). These nine cancers were also characterized by large intercellular variations in chromosome copy numbers that were not detected in the 27 major diploid type cancers. The aneuploid cancer group included only three subtype tumors that showed only a small number of DCNAs (mean, 3 per tumor) and minimal intercellular variations in chromosomal copy number. These data indicate that gastric adenocarcinomas can be divided into three types; aneuploid, major diploid type and diploid subtype cancers. Large-scale studies are necessary to clarify the differences in biological characteristics and underlying genetic mechanisms between these types.

Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers

“…PTPRS has been shown to directly interact with and dephosphorylate EGFR (34,35). We observed deletions in this gene that were highly focal, robustly identifying PTPRS as the target of CNA on chromosome 19p13.3, a genomic region frequently lost in several cancers and thought to harbor an as-yet-unidentified tumor suppressor (36)(37)(38)(39). Interestingly, several unique tumors had similar deletions, suggesting that loss of these regions may be highly selected in HNSCC.…”

Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versushistologic macrodissection

“…Array CGH analysis was performed using genomic DNA extracted from macrodissected samples containing > 50% tumor cells (criteria used by previous studies [16,17]) since sufficient DNA could be obtained without the need for whole genome amplification as required for microdissected samples. Whole genome DNA amplification may potentially introduce artifactual bias in array CGH results [18].…”

Clinical applications of slide‐based cytometry – an update

“…In primary lung adenocarcinomas, the number of DNA copy number aberrations (DCNAs) was closely related to DNA aneuploidy (Hayashi et al [38]). However, this was not found in gastric adenocarcinomas where DCNAs were common in aneuploid as well as in a subset of diploid tumors (Furuya et al [39]). Whereas it could be confirmed further down the digestive road, i.e.…”