The effects of mutational processes and selection on driver mutations across cancer types

Nature Communications
Daniel TemkoTrevor A Graham

Abstract

Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data from 11,336 cancers of various types to infer the independent effects of mutation and selection on the set of driver mutations in a cancer type. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes have a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.

References

Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·A J RowanI P Tomlinson
Mar 1, 1954·British Journal of Cancer·P ARMITAGE, R DOLL
Aug 2, 2005·Nature Reviews. Cancer·Oliver M SieberIan P M Tomlinson
Sep 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gregory J RielyMarc Ladanyi
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ivana BozicMartin A Nowak
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Sep 28, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Snjezana DoganMarc Ladanyi
Jan 16, 2013·Cell Reports·Ludmil B AlexandrovMichael R Stratton
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Dec 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Cristian TomasettiBert Vogelstein
Feb 11, 2015·Nature Genetics·Andrea SottorivaChristina Curtis
Apr 2, 2015·Nature Communications·Matthew K H HongChristopher M Hovens
Apr 17, 2015·Science Translational Medicine·Nicholas McGranahanCharles Swanton
Jun 4, 2015·JAMA Surgery·Georgios Antonios MargonisTimothy M Pawlik
Oct 13, 2015·Nature Reviews. Cancer·Francesc Castro-GinerIan Tomlinson
Nov 10, 2015·Nature Genetics·Ludmil B AlexandrovMichael R Stratton
May 3, 2016·Nature·Serena Nik-ZainalMichael R Stratton
May 22, 2016·Carcinogenesis·Mia Petljak, Ludmil B Alexandrov
Oct 24, 2017·Cell·Iñigo MartincorenaPeter J Campbell
Nov 7, 2017·Nature Genetics·Donate Weghorn, Shamil Sunyaev

❮ Previous
Next ❯

Citations

Jun 5, 2019·Molecular Genetics & Genomic Medicine·Peter GeorgesonDaniel D Buchanan
Apr 15, 2020·Nature Communications·Siqi LiChristopher M Counter
Dec 26, 2019·Genome Biology·Pablo E García-NietoHunter B Fraser
Jan 12, 2020·Communications Biology·Xiaobao DongMulin Jun Li
Jul 30, 2020·Cancer Metastasis Reviews·Jozsef Timar, Karl Kashofer
May 7, 2019·Annual Review of Genomics and Human Genetics·Marc J WilliamsTrevor A Graham
Nov 15, 2019·Nature Communications·Priyanka GopalMohamed E Abazeed
Jul 6, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Jing WangZhiyong Liang
Sep 16, 2020·Nature Genetics·Eszter LakatosTrevor A Graham
Jun 8, 2019·International Journal of Cancer. Journal International Du Cancer·Shengfeng WangOlufunmilayo I Olopade
Oct 9, 2020·Cancers·Caroline MolinaroKatia Cailliau
Jun 28, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher H LieuJoshua E Meyer
Mar 17, 2020·Bioinformatics·Pramod ChandrashekarLi Liu
Feb 19, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·R Barroso-SousaN Wagle
Nov 28, 2020·Trends in Cancer·Bruce GottliebGerald Batist
May 22, 2021·Nature Ecology & Evolution·Andrew WoolstonMarco Gerlinger
Oct 6, 2020·NAR Cancer·Xiaoju HuSubhajyoti De
May 18, 2021·ELife·Siqi Li, Christopher M Counter
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Anna Julia WiecekMaria Secrier
Sep 16, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Rony F ArauzBríd M Ryan
Sep 15, 2021·Cancer Discovery·Marie J ParsonsLukas E Dow
Oct 7, 2021·Environmental Science and Pollution Research International·Smita KumariRashmi K Ambasta
Nov 9, 2021·Frontiers in Genetics·Axel Rosendahl HuberRuben Van Boxtel

❮ Previous
Next ❯

Software Mentioned

R package ‘ SomaticSignatures ’
R package ‘ nnls ’
Annovar

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Epidemiology of Aging

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Cancer Imaging

Imaging techniques, including CT and MR, have become essential to tumor detection, diagnosis, and monitoring. Here is the latest research on cancer imaging.

Aging Epidemiology

This feed focuses on epidemiology of aging and aging-related conditions, including Alzheimer’s disease, dementia, and age-associated cognitive impairment. Here is the latest research.

Related Papers

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Aung Ko WinMark A Jenkins
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Leeanne J MeadMelissa C Southey
© 2022 Meta ULC. All rights reserved