title: Genomic Alteration During Metastasis of Lung Adenocarcinoma.
abstract: OBJECTIVE
  Recurrent gene mutation has been identified by the analysis of exonic DNA from lung adenocarcinoma, but its progression has not been extensively profiled. The investigation of the mutational landscape of tumors provides new insights into cancer genome evolution and further discovers the interplay of somatic mutation, adaptation of clones to their environment and natural selection. Cancer development involves cycles of genomic damage, epigenetic deregulation, and increased cellular proliferation that eventually culminate in the carcinoma phenotype.
  
  
  METHODS
  Comparative whole exome sequencing of both primary and metastatic tumor tissues from four patients of stage IV lung adenocarcinoma patients with chest wall metastasis was performed. Both primary and metastatic tumors were diagnosed through biopsy followed by surgical resection. All tumor specimens were cut into several pieces to assess potential heterogenic clones within the tumor tissue. Adjacent normal lung tissue was also obtained to provide germline mutation background.
  
  
  RESULTS
  By modeling and analyzing progression of the cancer metastasis based on non-synonymous variants, we defined the extent of heterogeneity of cancer genomes and identified similar cancer evolution pattern in the four patients: metastasis was an early event occurring right after the primary cancer formation and evolution in the metastatic tumor was continuously and simultaneously in progression with that in the primary tumor. By characterizing the clonal hierarchy of genetic lesions, we further charted a pathway of oncogenic events along which genes may drive lung adenocarcinoma metastasis, such as TAS2R31 and UMODL1, involving in G-protein coupled receptor protein signaling pathway.
  
  
  CONCLUSIONS
  The candidate genes identified in this study may become targets for the treatment of lung adenocarcinoma metastasis.
authors.affiliation: Department of Shanghai Lung Tumor Clinic Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Ding
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Niu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Li
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Luo
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D004252:DNA Mutational Analysis; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D010802:Phylogeny