title: Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients.
abstract: Lung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-κB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease.
authors.affiliation: 1] State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China [2].
authors.forename: Shanye
authors.initials: S
authors.lastname: Yin
authors.affiliation: 1] State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China [2].
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China [2].
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.affiliation: 1] State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China [2].
authors.forename: Wenjun
authors.initials: W
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
authors.forename: Xianfu
authors.initials: X
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, People's Republic of China.
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Wu
authors.affiliation: Shanghai-MOST Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, People's Republic of China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
authors.affiliation: Department of pathology, Shanghai Chest Hospital, Shanghai 200025, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
authors.forename: Landian
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, People's Republic of China.
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
mesh_terms: D044466:Asian People / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002681:China; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D059645:Mutation Rate; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins
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