title: Genome-wide mutation profiles of colorectal tumors and associated liver metastases at the exome and transcriptome levels.
abstract: 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.
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
authors.forename: Byungho
authors.initials: B
authors.lastname: Lim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Jihyeob
authors.initials: J
authors.lastname: Mun
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Chan Wook
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.|Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Seon Ae
authors.initials: SA
authors.lastname: Roh
authors.affiliation: Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.|Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Republic of Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.|Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.|Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.|Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Jin Cheon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D059472:Exome; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D009154:Mutation; D009362:Neoplasm Metastasis; D059467:Transcriptome
keywords: RNA sequencing; colorectal cancer; exome sequencing; liver metastasis; somatic mutation