Research Papers:

A genome-wide assessment of rare copy number variants in colorectal cancer

Zhenli Li, Dan Yu, Meifu Gan, Qiaonan Shan, Xiaoyang Yin, Shunli Tang, Shuai Zhang, Yongyong Shi, Yimin Zhu, Maode Lai and Dandan Zhang _

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Oncotarget. 2015; 6:26411-26423. https://doi.org/10.18632/oncotarget.4621

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Zhenli Li1,2, Dan Yu1,2, Meifu Gan3, Qiaonan Shan4, Xiaoyang Yin4, Shunli Tang4, Shuai Zhang1,2, Yongyong Shi5, Yimin Zhu6, Maode Lai1,2, Dandan Zhang1,2

1Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China

2Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, 310058, China

3Department of Pathology, Taizhou Hospital, Linhai, Zhejiang, 317000, China

4Zhejiang University School of Clinical Medicine, Hangzhou, Zhejiang, 310058, China

5Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200000, China

6Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, 310058, China

Correspondence to:

Dandan Zhang, e-mail: [email protected]

Maode Lai, e-mail: [email protected]

Keywords: colorectal cancer, rare CNVs, genome-wide scan, nucleosome assembly

Received: April 03, 2015     Accepted: July 06, 2015     Published: July 20, 2015


Colorectal cancer (CRC) is a complex disease with an estimated heritability of approximately 35%. However, known CRC-related common single nucleotide polymorphisms (SNPs) can only explain ~0.65% of the heritability. This “missing heritability” may be explained partially by rare copy number variants (CNVs). In this study, we performed a genome-wide scan using Illumina Human-Omni Express BeadChip, 694 sporadic CRC cases and 1641 controls were eventually included in our analysis after quality control. The global burden analysis revealed a 1.53-fold excess of rare CNVs in CRC cases compared with controls (P < 1 × 10−6), and the difference being more pronounced for genic rare CNVs and CNVs overlapped with coding regions (1.65-fold and 1.84-fold, respectively, both P < 1 × 10−6). Interestingly, both the cases in the lowest and middle tertile of age carried a higher burden of rare CNVs comparing to the highest tertile. Furthermore, 639 CNV-disrupted genes exclusive to CRC cases were found to be significantly enriched in gene ontology (GO) terms concerning nucleosome assembly and olfactory receptor activity. Our study was the first to evaluate the burden of rare CNVs in sporadic CRC and suggested that rare CNVs contributed to the missing heritability of CRC.

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