Mutation spectrum in human colorectal cancers and potential functional relevance

Hongzhuan Yin,Qi Su,Baolin Liu,Zhaopeng Yan,Yichao Liang

doi:10.1186/1471-2350-14-32

Abstract

BackgroundSomatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle.MethodsIn order to understand the role of somatic mutations in human colorectal cancers, we characterized the mutation spectrum in two colorectal tumor tissues and their matched normal tissues, by analyzing deep-sequenced transcriptome data.ResultsWe found a higher mutation rate of somatic variants in tumor tissues in comparison with normal tissues, but no trend was observed for mutation properties. By applying a series of stringent filters, we identified 418 genes with tumor specific disruptive somatic variants. Of these genes, three genes in mucin protein family (MUC2, MUC4, and MU12) are of particular interests. It has been reported that the expression of mucin proteins was correlated with the progression of colorectal cancer therefore somatic variants within those genes can interrupt their normal expression and thus contribute to the tumorigenesis.ConclusionsOur findings provide evidence of the utility of RNA-Seq in mutation screening in cancer studies, and suggest a list of candidate genes for future colorectal cancer diagnosis and treatment.

Highlights

Somatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle
As the third most common malignancy and the fourth major cause of cancer mortality [1], colorectal cancer is an important threat to human health which accounts for 1 million new cases worldwide each year
Only a few common lowpenetrance variants attributing to cancer risk have been identified using genome-wide association studies (GWAS), and it is still largely unknown to us the underlying mechanisms and genes involved in tumor development

Summary

Introduction

Somatic variants, which occur in the genome of all cells, are well accepted to play a critical role in cancer development, as their accumulation in genes could affect cell proliferations and cell cycle. The consistency between incidence rates and economic development reflects a westernized lifestyle and attendant risk factor exposures [1]. Colorectal tumor progression is associated with both genetic and environmental factors. Only a few common lowpenetrance variants attributing to cancer risk have been identified using genome-wide association studies (GWAS), and it is still largely unknown to us the underlying mechanisms and genes involved in tumor development. The importance of somatic mutations in cancer development has been widely accepted. It is thought that cancer evolves through the accumulation of somatic mutations in specific genes, depending on various tumor

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