Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma
McFadden, David G.1,12,13; Politi, Katerina2,3,4; Bhutkar, Arjun1; Chen, Frances K.1; Song, Xiaoling4,14; Pirun, Mono5; Santiago, Philip M.1; Kim-Kiselak, Caroline1; Platt, James T.4; Lee, Emily6; Hodges, Emily6; Rosebrock, Adam P.6,15; Bronsong, Roderick T.7; Socci, Nicholas D.5; Hannon, Gregory J.6,8,16; Jacks, Tyler1,9,10; Varmus, Harold11,17
2016-10-18
Source PublicationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
Volume113Issue:42Pages:E6409-E6417
Status已发表
DOI10.1073/pnas.1613601113
AbstractGenetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC protooncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.
KeywordKRAS EGFR MYC GEMM exome
Indexed BySCI
Language英语
Funding ProjectCancer Research UK[21143]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000385610400014
PublisherNATL ACAD SCIENCES
WOS KeywordGENOMIC LANDSCAPE ; CANCER ; PROGRESSION ; SENSITIVITY ; ONCOGENE ; REARRANGEMENTS ; TUMORIGENESIS ; MAINTENANCE ; ACTIVATION ; EXPRESSION
Original Document TypeArticle
Citation statistics
Cited Times:89[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1668
Collection免疫化学研究所_特聘教授组_干细胞生物学实验室
免疫化学研究所_特聘教授组_抗体化学实验室
Corresponding AuthorMcFadden, David G.; Politi, Katerina
Affiliation1.MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
2.Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA
3.Yale Univ, Sch Med, Dept Med, Sect Med Oncol, New Haven, CT 06510 USA
4.Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT 06510 USA
5.Mem Sloan Kettering Canc Ctr, Bioinformat Core, New York, NY 10065 USA
6.Cold Spring Harbor Lab, Watson Sch Biol Sci, POB 100, Cold Spring Harbor, NY 11724 USA
7.Tufts Univ, Sch Med & Vet Med, Dept Pathol, North Grafton, MA 01536 USA
8.Cold Spring Harbor Lab, Howard Hughes Med Inst, POB 100, Cold Spring Harbor, NY 11724 USA
9.MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
10.MIT, Dept Biol, Cambridge, MA 02142 USA
11.Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10065 USA
12.UT Southwestern Med Ctr Dallas, Div Endocrinol, Dept Internal Med, Dallas, TX 75235 USA
13.UT Southwestern Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75235 USA
14.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
15.Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 1A1, Canada
16.Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England
17.Cornell Univ, Meyer Canc Ctr, Weill Cornell Med, New York, NY 10065 USA
Recommended Citation
GB/T 7714
McFadden, David G.,Politi, Katerina,Bhutkar, Arjun,et al. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2016,113(42):E6409-E6417.
APA McFadden, David G..,Politi, Katerina.,Bhutkar, Arjun.,Chen, Frances K..,Song, Xiaoling.,...&Varmus, Harold.(2016).Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,113(42),E6409-E6417.
MLA McFadden, David G.,et al."Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113.42(2016):E6409-E6417.
Files in This Item: Download All
File Name/Size DocType Version Access License
10.1073@pnas.1613601(947KB)期刊论文出版稿开放获取UnknownView Download
Related Services
Usage statistics
Scholar Google
Similar articles in Scholar Google
[McFadden, David G.]'s Articles
[Politi, Katerina]'s Articles
[Bhutkar, Arjun]'s Articles
Baidu academic
Similar articles in Baidu academic
[McFadden, David G.]'s Articles
[Politi, Katerina]'s Articles
[Bhutkar, Arjun]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[McFadden, David G.]'s Articles
[Politi, Katerina]'s Articles
[Bhutkar, Arjun]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: 10.1073@pnas.1613601113.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.