Publication Date:
2014-10-11
Description:
Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354858/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354858/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Jianjun -- Fujimoto, Junya -- Zhang, Jianhua -- Wedge, David C -- Song, Xingzhi -- Zhang, Jiexin -- Seth, Sahil -- Chow, Chi-Wan -- Cao, Yu -- Gumbs, Curtis -- Gold, Kathryn A -- Kalhor, Neda -- Little, Latasha -- Mahadeshwar, Harshad -- Moran, Cesar -- Protopopov, Alexei -- Sun, Huandong -- Tang, Jiabin -- Wu, Xifeng -- Ye, Yuanqing -- William, William N -- Lee, J Jack -- Heymach, John V -- Hong, Waun Ki -- Swisher, Stephen -- Wistuba, Ignacio I -- Futreal, P Andrew -- CA016672/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA070907/CA/NCI NIH HHS/ -- P50CA70907/CA/NCI NIH HHS/ -- T32 CA-009666/CA/NCI NIH HHS/ -- T32 CA009666/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2014 Oct 10;346(6206):256-9. doi: 10.1126/science.1256930.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Applied Cancer Science Institute, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. ; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Honorary Faculty, Wellcome Trust Sanger Institute, Hinxton, UK CB10 1SA. afutreal@mdanderson.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25301631" target="_blank"〉PubMed〈/a〉
Keywords:
Adenocarcinoma/*genetics/pathology
;
DNA Mutational Analysis
;
Exome/genetics
;
Genes, Neoplasm
;
*Genetic Heterogeneity
;
Humans
;
Lung Neoplasms/*genetics/pathology
;
Mutation
;
Neoplasm Recurrence, Local/*genetics/pathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
