Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients

Abstract

ABSTRACT. Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available singlenucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.

Quantitative analysis of somatically acquired and constitutive uniparental disomy in gastrointestinal cancers

“…In particular, we could show that STAD, EAC and ESCC carried significantly different patterns of aUPD compared to COAD and READ, thus suggesting the existence of cancer‐specific landscapes of aUPD across GI cancers. As observed for CNAs, aUPD profiles in the COAD cohort matched with those identified in READ samples, which is in agreement with previous reports . Remarkably, the high rate of segmental aUPD in STAD and ESCA suggests higher levels of structural CIN in these cancer types compared to COAD and READ, which agrees with a previous study showing more focal amplification events in the upper than in the lower GI tract .…”

“…As observed for CNAs, aUPD profiles in the COAD cohort matched with those identified in READ samples, which is in agreement with previous reports. 11,18,[33][34][35] Remarkably, the high rate of segmental aUPD in STAD and ESCA suggests higher levels of structural CIN in these cancer types compared to COAD and READ, which agrees with a previous study showing more focal amplification events in the upper than in the lower GI tract. 36 Furthermore, most GI cancers contain aneuploid genomes.…”