Genomic profiling of gastric carcinoma in situ and adenomas by array‐based comparative genomic hybridization

Abstract

Although genomic copy number aberrations (CNAs) of gastric carcinoma at the advanced stage have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis, those of gastric carcinoma in situ (CIS) are still poorly understood. Furthermore, no reports have demonstrated correlations between CNAs and histopathological features of gastric adenoma. In this study, we investigated CNAs of 20 gastric CISs (Vienna category 4.2) and 20 adenomas including seven low-grade adenomas (LGA; Vienna category 3) and 13 high-grade adenomas (HGA; Vienna category 4.1), using oligonucleotide-based array CGH. The most frequent aberrations in CIS were gains at 8q (85%) and 20q (50%), and losses at 5q (50%) and 17p (50%), suggesting that these CNAs are involved in the development of CIS. We found that the pattern of CNAs in HGA was quite different from that in LGA. The most frequent CNAs in HGA were gains at 8q (62%) and 7pq (54%), whereas those in LGA were gain at 7q21.3-q22.1 (57%) and loss at 5q (43%). Interestingly, gains at 8q and 7pq, both of which occurred most frequently in HGA, were not detected in any cases of LGA. Of note, 8q gain was detected most frequently in both HGA and CIS but was undetected in LGA. Since HGA is believed to have a higher risk of progression to invasive carcinoma than LGA, these data suggest that 8q gain is important for the malignant transformation of gastric adenoma.

Rapidly and Slowly Growing Lineages in Chromosomal Instability-Type Gland-Forming Gastric Carcinomas as Revealed by Multisampling Analysis of DNA Copy-Number Profile

“…Both lineages could have derived from a common trunk with 8q+, 13q+, 20p/q+, and 5q−, commonly detected in both cluster A and cluster B. These findings partly confirm the report of Uchida et al [18], who reported 8p± and 5q− as early changes of GC, and then cluster-specific later changes, such as 7pq+ in cluster A and 4pq− in cluster B (Fig. 4).…”

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

“…Several studies have revealed that genetic alterations begin in the early stages of cancer and even in precancerous lesions. Early studies using CGH arrays suggested that an 8q gain in HGIN may play a pivotal role in the development of gastric carcinoma [7] . However, the gene expression levels and functions associated with the copy number status of 8q were not detailed.…”

“…Based on the potential transition between and morphological similarity of dysplasia and carcinoma, the hypothesis that they are biologically related is reasonable. Previous studies of the genomic copy number aberration of gastric precancerous lesions and carcinoma in situ (CIS) have provided the most prominent 8q gain, which was detected most frequently in both HGIN and CIS but was undetected in LGIN using array comparative genomic hybridization [7] . Therefore, evidence has shown that molecular variations in gastric carcinogenesis have already appeared in precancerous lesions or EGC.…”

The Association between DNA Copy Number Aberrations at Chromosome 5q22 and Gastric Cancer

“…Most frequent losses of the copy number at 5q22 in GC patients of difference racial are summarized in Table S1 in File S1 [8]–[10], [12], [13], [17]–[22]. Studies reported that 15.4% in Japanese [10], 35% in Korean [21], and 21% in Turk [20] of GC patients had gene mutations at 5q14–22.…”