Research Papers:

Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels

Byungho Lim _, Jihyeob Mun, Jeong-Hwan Kim, Chan Wook Kim, Seon Ae Roh, Dong-Hyung Cho, Yong Sung Kim, Seon-Young Kim and Jin Cheon Kim

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Oncotarget. 2015; 6:22179-22190. https://doi.org/10.18632/oncotarget.4246

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Byungho Lim1, Jihyeob Mun1,2, Jeong-Hwan Kim1, Chan Wook Kim3, Seon Ae Roh3,4, Dong-Hyung Cho4,5, Yong Sung Kim1,2,4, Seon-Young Kim1,2, Jin Cheon Kim3,4

1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea

2Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea

3Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea

4Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea

5Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Republic of Korea

Correspondence to:

Jin Cheon Kim, e-mail: [email protected]

Seon-Young Kim, e-mail: [email protected]

Keywords: colorectal cancer, exome sequencing, liver metastasis, RNA sequencing, somatic mutation

Received: March 17, 2015     Accepted: May 18, 2015     Published: June 01, 2015


To characterize the mutation profiles of colorectal cancer (CRC) primary tumors (PTs) and liver metastases (CLMs), we performed both whole-exome and RNA sequencing. Ten significantly mutated genes, including BMI1, CARD11, and NRG1, were found in 34 CRCs with CLMs. We defined three mutation classes (Class 1 to 3) based on the absence or presence of mutations during liver metastasis. Most mutations were classified into Class 1 (shared between PTs and CLMs), suggesting the common clonal origin of PTs and CLMs. Class 1 was more strongly associated with the clinical characteristics of advanced cancer and was more frequently superimposed with chromosomal deletions in CLMs than Class 2 (PT-specific). The integration of exome and RNA sequencing revealed that variant-allele frequencies (VAFs) of mutations in the transcriptome tended to have stronger functional implications than those in the exome. For instance, VAFs of the TP53 and APC mutations in the transcriptome significantly correlated with the expression level of their target genes. Additionally, mutations with high functional impact were enriched with high VAFs in the CLM transcriptomes. We identified 11 mutation-associated splicing events in the CRC transcriptomes. Thus, the integration of the exome and the transcriptome may elucidate the underlying molecular events responsible for CLMs.

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