Genomic landscape and evolution of arm aneuploidy in lung adenocarcinoma

Neoplasia: An International Journal for Oncology Research

Changhong Liu¹  Zhe Zhang²  Fujun Yang³  Beili Gao⁴  Ming Han⁵  Yang Shao⁵  Yi Shen⁵  Xue Wu⁵  Hua Bao⁵  Ran Cao⁵ 

[1] School of Public Health, Nanjing Medical University, Nanjing, China;Corresponding authors.;Department of Oncology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China;Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;Nanjing Geneseeq Technology Inc. Nanjing, Jiangsu, China;

关键词: Lung adenocarcinoma;    Chromosome arm aneuploidy;    Metastatic sites;    EGFR;    Mutations;    Arm aneuploidy evolution;   

DOI  :  

来源: DOAJ

【 摘 要 】

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Moreover, EGFR, MET, PIK3CA, PKHD1 and RB1 mutant groups were found to have high CAA burden, while those with BRAF, ERBB2 and KRAS mutations belonged to the low CAA burden group. Comparing EGFR L858R and EGFR 19del mutants, distinct CAA co-occurrences were observed. Network-based stratification with population based genomic evolution analysis revealed two distinct subtypes of LUAD with different CAA signatures and unique CAA order of acquisition. In summary, our study presented a comprehensive characterization of arm aneuploidy landscape and evolutionary trajectories in lung adenocarcinoma, which could provide basis for both biological and clinical investigations in the future.

【 授权许可】

Unknown