title: Leveraging a Multi-Omics Strategy for Prioritizing Personalized Candidate Mutation-Driver Genes: A Proof-of-Concept Study.
abstract: The expression of mutant forms of proteins (e.g., oncogenes and tumor suppressors) has implications in cancer biology and clinical practice. Initial efforts have been made to characterize the transcription of tumor-mutated alleles; however, few studies have been reported to link tumor-mutated alleles to proteomics. We aimed to characterize the transcriptional and translational patterns of tumor-mutated alleles. We performed whole-exome sequencing, RNA-seq, and proteome profiling in a hyper-mutated patient of hepatocellular carcinoma. Using the patient as a model, we show that only a small proportion of tumor-mutated alleles were expressed. In this case, 42% and 3.5% of the tumor-mutated alleles were identified to be transcribed and translated, respectively. Compared with genes with germline variations or without mutations, somatic mutations significantly reduced protein expression abundance. Using the transcriptional and translational patterns of tumor-mutated alleles, we classified the mutations into four types, and only one type may be associated with the liver cancer and lead to hepatocarcinogenesis in the patient. Our results demonstrate how tumor-mutated alleles are transcribed and translated, and how the expression enables the classification of somatic mutations that cause cancer. Leveraging multiple 'omics' datasets provides a new avenue for understanding patient-specific mutations that underlie carcinogenesis.
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education of China; Depeartment of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China, 400010.
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Songfeng
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Wantao
authors.initials: W
authors.lastname: Ying
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education of China; Depeartment of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China, 400010.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China, 100730.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China, 100730.
authors.forename: Dachun
authors.initials: D
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Xianyu
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education of China; Depeartment of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China, 400010.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Proteomics, National Protein Science Beijing Center, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P.R. China, 102206.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Qian
mesh_terms: D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D057285:Precision Medicine / Q000379:methods*; D020543:Proteome / Q000235:genetics; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA
chemical_list: D020543:Proteome; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein