Mutation pattern analysis reveals polygenic mini-drivers associated with relapse after surgery in lung adenocarcinoma
AffiliationRNA Biology Group, CRUK Manchester Institute, The University of Manchester, Alderley Park, Manchester, SK10 4TG, UK
MetadataShow full item record
AbstractThe genomic lesions found in malignant tumours exhibit a striking degree of heterogeneity. Many tumours lack a known driver mutation, and their genetic basis is unclear. By mapping the somatic mutations identified in primary lung adenocarcinomas onto an independent coexpression network derived from normal tissue, we identify a critical gene network enriched for metastasis-associated genes. While individual genes within this module were rarely mutated, a significant accumulation of mutations within this geneset was predictive of relapse in lung cancer patients that have undergone surgery. Since it is the density of mutations within this module that is informative, rather than the status of any individual gene, these data are in keeping with a 'mini-driver' model of tumorigenesis in which multiple mutations, each with a weak effect, combine to form a polygenic driver with sufficient power to significantly alter cell behaviour and ultimately patient outcome. These polygenic mini-drivers therefore provide a means by which heterogeneous mutation patterns can generate the consistent hallmark changes in phenotype observed across tumours.
CitationBennett L, Howell M, Memon D, Smowton C, Zhou C, Miller CJ. Mutation pattern analysis reveals polygenic mini-drivers associated with relapse after surgery in lung adenocarcinoma. Scientific Reports [Internet]. 2018 Oct 4;8(1).
- The mini-driver model of polygenic cancer evolution.
- Authors: Castro-Giner F, Ratcliffe P, Tomlinson I
- Issue date: 2015 Nov
- Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study.
- Authors: Shi J, Hua X, Zhu B, Ravichandran S, Wang M, Nguyen C, Brodie SA, Palleschi A, Alloisio M, Pariscenti G, Jones K, Zhou W, Bouk AJ, Boland J, Hicks B, Risch A, Bennett H, Luke BT, Song L, Duan J, Liu P, Kohno T, Chen Q, Meerzaman D, Marconett C, Laird-Offringa I, Mills I, Caporaso NE, Gail MH, Pesatori AC, Consonni D, Bertazzi PA, Chanock SJ, Landi MT
- Issue date: 2016 Dec
- MET exon 14 skipping mutation in triple-negative pulmonary adenocarcinomas and pleomorphic carcinomas: An analysis of intratumoral MET status heterogeneity and clinicopathological characteristics.
- Authors: Kwon D, Koh J, Kim S, Go H, Kim YA, Keam B, Kim TM, Kim DW, Jeon YK, Chung DH
- Issue date: 2017 Apr
- Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity.
- Authors: Løvf M, Zhao S, Axcrona U, Johannessen B, Bakken AC, Carm KT, Hoff AM, Myklebost O, Meza-Zepeda LA, Lie AK, Axcrona K, Lothe RA, Skotheim RI
- Issue date: 2019 Mar
- Genomic heterogeneity of multiple synchronous lung cancer.
- Authors: Liu Y, Zhang J, Li L, Yin G, Zhang J, Zheng S, Cheung H, Wu N, Lu N, Mao X, Yang L, Zhang J, Zhang L, Seth S, Chen H, Song X, Liu K, Xie Y, Zhou L, Zhao C, Han N, Chen W, Zhang S, Chen L, Cai W, Li L, Shen M, Xu N, Cheng S, Yang H, Lee JJ, Correa A, Fujimoto J, Behrens C, Chow CW, William WN, Heymach JV, Hong WK, Swisher S, Wistuba II, Wang J, Lin D, Liu X, Futreal PA, Gao Y
- Issue date: 2016 Oct 21