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

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...

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Bibliographic Details
Published in:Genetics and molecular research 2013-02, Vol.12 (1), p.319-327
Main Authors: Yam, Y Y, Hoh, B P, Othman, N H, Hassan, S, Yahya, M M, Zakaria, Z, Ankathil, R
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Asian Continental Ancestry Group - genetics
Chromosome Aberrations
Colorectal Neoplasms - genetics
Disease Progression
DNA Copy Number Variations
Female
Genotype
Humans
Loss of Heterozygosity
Malaysia
Male
Microsatellite Instability
Middle Aged
Polymorphism, Single Nucleotide
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Summary: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 single-nucleotide 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.
ISSN:1676-5680
1676-5680
DOI:10.4238/2013.February.7.1