Minimal functional driver gene heterogeneity among untreated metastases
Johannes G. Reiter,Johannes G. Reiter,Alvin Makohon-Moore,Jeffrey M. Gerold,Alexander Heyde,Marc A. Attiyeh,Zachary A. Kohutek,Collin Tokheim,Alexia Brown,Rayne M. DeBlasio,Juliana Niyazov,Amanda Zucker,Rachel Karchin,Rachel Karchin,Kenneth W. Kinzler,Christine A. Iacobuzio-Donahue,Bert Vogelstein,Martin A. Nowak +17 more
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TLDR
Within individual patients, a large majority of driver gene mutations are common to all metastases, and a mathematical model of tumor evolution and metastasis formation provides an explanation for the observed driver gene homogeneity.Abstract:
Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, heterogeneity among treatment-naive metastases has not been comprehensively assessed. We analyzed sequencing data for 76 untreated metastases from 20 patients and inferred cancer phylogenies for breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, and prostate cancers. We found that within individual patients, a large majority of driver gene mutations are common to all metastases. Further analysis revealed that the driver gene mutations that were not shared by all metastases are unlikely to have functional consequences. A mathematical model of tumor evolution and metastasis formation provides an explanation for the observed driver gene homogeneity. Thus, single biopsies capture most of the functionally important mutations in metastases and therefore provide essential information for therapeutic decision-making.read more
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SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer
TL;DR: A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell.
Journal ArticleDOI
Pan-cancer whole-genome analyses of metastatic solid tumours
Peter Priestley,Jonathan Baber,Martijn P. Lolkema,Neeltje Steeghs,Ewart de Bruijn,Charles Shale,Korneel Duyvesteyn,Susan Haidari,Arne Van Hoeck,Wendy Onstenk,Paul Roepman,Mircea Voda,Haiko J. Bloemendal,Vivianne C. G. Tjan-Heijnen,Carla M.L. van Herpen,Mariette Labots,Petronella O. Witteveen,Egbert F. Smit,Stefan Sleijfer,Emile E. Voest,Edwin Cuppen +20 more
TL;DR: The largest, to the authors' knowledge, pan-cancer study of metastatic solid tumour genomes, including whole-genome sequencing data for 2,520 pairs of tumour and normal tissue pairs, analysed at median depths of 106× and 38×, respectively, and surveying more than 70 million somatic variants is described.
Journal ArticleDOI
Tumour evolution in hepatocellular carcinoma.
Amanda J. Craig,Johann von Felden,Johann von Felden,Teresa Garcia-Lezana,Samantha Sarcognato,Samantha Sarcognato,Augusto Villanueva +6 more
TL;DR: The molecular heterogeneity of hepatocellular carcinoma, the intrinsic and extrinsic factors that stimulate tumour evolution and how this information can be leveraged to improve the clinical management of patients with this disease are discussed.
Journal ArticleDOI
Resolving genetic heterogeneity in cancer.
Samra Turajlic,Samra Turajlic,Andrea Sottoriva,Trevor A. Graham,Charles Swanton,Charles Swanton +5 more
TL;DR: An overview of the theoretical models of tumour evolution is provided and what to consider when inferring evolutionary dynamics from genomic data is discussed.
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Context is everything: aneuploidy in cancer
Uri Ben-David,Angelika Amon +1 more
TL;DR: The context dependency of aneuploidy in cancer is explained and its clinical potential is discussed, which may have clinical relevance as a prognostic marker and as a potential therapeutic target.
References
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Journal ArticleDOI
A genetic model for colorectal tumorigenesis
Eric R. Fearon,Bert Vogelstein +1 more
TL;DR: A model for the genetic basis of colorectal neoplasia that includes the following salient features is presented, which may be applicable to other common epithelial neoplasms, in which tumors of varying stage are more difficult to study.
Journal ArticleDOI
A method and server for predicting damaging missense mutations.
Ivan Adzhubei,Steffen Schmidt,Leonid Peshkin,Vasily Ramensky,Anna Gerasimova,Peer Bork,Alexey S. Kondrashov,Shamil R. Sunyaev +7 more
TL;DR: A new method and the corresponding software tool, PolyPhen-2, which is different from the early tool polyPhen1 in the set of predictive features, alignment pipeline, and the method of classification is presented and performance, as presented by its receiver operating characteristic curves, was consistently superior.
Journal ArticleDOI
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
Marco Gerlinger,Andrew Rowan,Stuart Horswell,James Larkin,David Endesfelder,Eva Grönroos,Pierre Martinez,Nicholas Matthews,Aengus Stewart,Patrick S. Tarpey,Ignacio Varela,Benjamin Phillimore,Sharmin Begum,Neil Q. McDonald,Adam Butler,David T. Jones,Keiran Raine,Calli Latimer,Claudio R. Santos,Mahrokh Nohadani,Aron Charles Eklund,Bradley Spencer-Dene,Graham Clark,Lisa Pickering,Gordon Stamp,Martin Gore,Zoltan Szallasi,Zoltan Szallasi,Julian Downward,P. Andrew Futreal,Charles Swanton +30 more
TL;DR: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development.
Journal ArticleDOI
Cancer Genome Landscapes
Bert Vogelstein,Nickolas Papadopoulos,Victor E. Velculescu,Shibin Zhou,Luis A. Diaz,Kenneth W. Kinzler +5 more
TL;DR: This work has revealed the genomic landscapes of common forms of human cancer, which consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of "hills" (Genes altered infrequently).
Journal ArticleDOI
The clonal evolution of tumor cell populations
TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
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