title: The genomic dynamics during progression of lung adenocarcinomas.
abstract: Intra-tumor heterogeneity is a big barrier to precision medicine. To explore the underlying clonal diversity in lung adenocarcinomas, we selected nine individuals with whole-genome sequencing data from primary and matched metastatic tumors as a cohort for study. Similar global pattern of arm-level copy number changes and large variations of somatic single-nucleotide variant between the primary and metastasis are observed in the majority of cases. Importantly, we found breakage-fusion-bridge (BFB) cycles acting as an important mechanism for underlying cancer gene amplification, such as amplification of CDK4, CDKN3 and FGFR1 in early stage. We also identified recurrent focal amplification of gene CCNY derived from BFB in two metastatic tumors, but not in primary tumor. Clonal analysis of case 236T demonstrated that mutational processes are varying with tumor progression. Collectively, our data provide new insights into genetic diversity and potential therapeutic target in lung adenocarcinoma.
authors.affiliation: Department of Breast surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Longhai
authors.initials: L
authors.lastname: Luo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Xiong
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Meng
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D014408:Biomarkers, Tumor / Q000235:genetics*; D056915:DNA Copy Number Variations; D018450:Disease Progression; D005784:Gene Amplification; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor