Genomic and Functional Approaches to Understanding Cancer Aneuploidy

AM Taylor; J Shih; G Ha; GF Gao; X Zhang; AC Berger; SE Schumacher; C Wang; H Hu; J Liu; AJ Lazar; SJ Caesar-Johnson; JA Demchok; I Felau; M Kasapi; ML Ferguson; CM Hutter; HJ Sofia; R Tarnuzzer; Z Wang; L Yang; JC Zenklusen; J Zhang; S Chudamani; J Liu; L Lolla; R Naresh; T Pihl; Q Sun; Y Wan; Y Wu; J Cho; T DeFreitas; S Frazer; N Gehlenborg; G Getz; DI Heiman; J Kim; MS Lawrence; P Lin; S Meier; MS Noble; G Saksena; D Voet; H Zhang; B Bernard; N Chambwe; V Dhankani; T Knijnenburg; R Kramer; K Leinonen; Y Liu; M Miller; S Reynolds; I Shmulevich; V Thorsson; W Zhang; R Akbani; BM Broom; AM Hegde; Z Ju; RS Kanchi; A Korkut; J Li; H Liang; S Ling; W Liu; Y Lu; GB Mills; KS Ng; A Rao; M Ryan; J Wang; JN Weinstein; J Zhang; A Abeshouse; J Armenia; D Chakravarty; WK Chatila; I de Bruijn; J Gao; BE Gross; ZJ Heins; R Kundra; K La; M Ladanyi; A Luna; MG Nissan; A Ochoa; SM Phillips; E Reznik; F Sanchez-Vega; C Sander; N Schultz; R Sheridan; SO Sumer; Y Sun; BS Taylor; J Wang; H Zhang

Journal article

Genomic and Functional Approaches to Understanding Cancer Aneuploidy

AM Taylor, J Shih, G Ha, GF Gao, X Zhang, AC Berger, SE Schumacher, C Wang, H Hu, J Liu, AJ Lazar, SJ Caesar-Johnson, JA Demchok, I Felau, M Kasapi, ML Ferguson, CM Hutter, HJ Sofia, R Tarnuzzer, Z Wang Show all

Cancer Cell | Published : 2018

DOI: 10.1016/j.ccell.2018.03.007

Abstract

Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic an..

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University of Melbourne Researchers

Christopher Hovens Author

Anthony Costello Author

Michael Lawrence Author

Alex Boussioutas Author

Grants

Awarded by Merck

Funding Acknowledgements

All cytogenomics analysis was performed by the CytoGenomics Core at Brigham and Women's Hospital. A plasmid containing an artificial telomere was kindly shared by Narumi Uno and Mitsuo Oshimura (Uno et al., 2017). A.M.T. was funded by grants from Uniting Against Lung Cancer and the Lung Cancer Research Foundation and is an American Cancer Society postdoctoral fellow (grant number 128194-PF-16-001-01-CCG). M.M. acknowledges support from the National Cancer Institute (1R35CA197568) and the Norman R. Seaman Endowment fund. M.M. is an American Cancer Society Research Professor (grant number 127046-RP-14-230-01-TBG). Funding sources for The Cancer Genome Atlas Research Network include: U54 HG003273 (PI Richard A. Gibbs), U54 HG003067 (PIs Stacey Gabriel and Eric S. Lander), U54 HG003079 (PI Richard K. Wilson), U24 CA143799 (PI Terence Paul Speed and Paul T. Spellman), U24 CA143835 (PI Ilya Shmulevich), U24 CA143840 (PIs Marc Ladanyi and Chris Sander), U24 CA143843 (PIs Richard A. Gibbs and David Andrew Wheeler), U24 CA143845 (PIs Lynda Chin and Gad Getz), U24 CA143848 (PI David N. Hayes and Charles M. Perou), U24 CA143858 (PIs Joshua Stuart, Christopher Benz, and David H. Haussler), U24 CA143866 (PI Marco Antonio Marra), U24 CA143867 (PI Stacey Gabriel and Matthew L. Meyerson), U24 CA143882 (PIs Stephen B. Baylin and Peter W. Laird), U24 CA143883 (PIs Gordon B. Mills, John N. Weinstein, Rehan Akbani, and W. K. Alfred Yung), U24 CA144025 (PI Raju S. Kucherlapati), and P30 CA016672 (PI Gordon B. Mills).