Interplay between DNA damage repair and apoptosis shapes cancer evolution through aneuploidy and microsatellite instability.

Nature Communications
Noam AuslanderEugene V Koonin

Abstract

Driver mutations and chromosomal aneuploidy are major determinants of tumorigenesis that exhibit complex relationships. Here, we identify associations between driver mutations and chromosomal aberrations that define two tumor clusters, with distinct regimes of tumor evolution underpinned by unique sets of mutations in different components of DNA damage response. Gastrointestinal and endometrial tumors comprise a separate cluster for which chromosomal-arm aneuploidy and driver mutations are mutually exclusive. The landscape of driver mutations in these tumors is dominated by mutations in DNA repair genes that are further linked to microsatellite instability. The rest of the cancer types show a positive association between driver mutations and aneuploidy, and a characteristic set of mutations that involves primarily genes for components of the apoptotic machinery. The distinct sets of mutated genes derived here show substantial prognostic power and suggest specific vulnerabilities of different cancers that might have therapeutic potential.

References

Sep 1, 1984·Journal of Clinical Pathology·M L FriedlanderI W Taylor
Jan 1, 1999·Nature·C LengauerB Vogelstein
Apr 20, 2001·The New England Journal of Medicine·T WatanabeS R Hamilton
May 18, 2001·Nature·G I Evan, K H Vousden
Mar 6, 2004·Cancer Metastasis Reviews·William M Grady
Nov 19, 2004·Nature·Michael B Kastan, Jiri Bartek
Nov 19, 2004·Nature·Harith Rajagopalan, Christoph Lengauer
Dec 23, 2004·Seminars in Cancer Biology·Manuel R Teixeira, Sverre Heim
Jan 4, 2006·Nature Cell Biology·Michael Downey, Daniel Durocher
Aug 29, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Yeganeh Ataian, Jocelyn E Krebs
Oct 19, 2006·Current Opinion in Cell Biology·Beth A A Weaver, Don W Cleveland
Jan 18, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·George P KimUNKNOWN National Cancer Institute
Mar 28, 2007·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Peter DuesbergRuediger Hehlmann
Aug 5, 2008·Trends in Genetics : TIG·Robin M RickeJan M van Deursen
May 12, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Gaëtan Des GuetzBernard Uzzan
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jan 29, 2011·Cancer Research·Nicolai J BirkbakCharles Swanton
Feb 15, 2011·Cell·Yun-Chi TangAngelika Amon
Mar 3, 2011·Cancer Research·Alvin J X LeeCharles Swanton
Mar 9, 2011·Nature Medicine·Lynda ChinP Andrew Futreal
Apr 22, 2011·Nature Reviews. Molecular Cell Biology·Jolien S Verdaasdonk, Kerry Bloom
Jul 6, 2011·Nucleic Acids Research·Boris RevaChris Sander
Jan 20, 2012·Nature·Christopher J Lord, Alan Ashworth
May 1, 2012·Nature Biotechnology·Scott L CarterGad Getz
Aug 17, 2012·Nature·Somasekar SeshagiriFrederic J de Sauvage
Oct 10, 2012·The Journal of Cell Biology·Alex PinesLeon Mullenders
Oct 12, 2012·PloS One·Yongwook ChoiAgnes P Chan
Nov 24, 2012·Nature Reviews. Cancer·Nicola J Curtin
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Sep 28, 2013·Nature Genetics·Giovanni CirielloChris Sander
Sep 28, 2013·Nature Genetics·Travis I ZackRameen Beroukhim
Jan 1, 2014·World Journal of Gastroenterology : WJG·Shigeo KoidoHisao Tajiri
Nov 14, 2014·Nucleic Acids Research·Mary GoldmanJingchun Zhu
Feb 19, 2015·Contemporary Oncology Współczesna Onkologia·Katarzyna TomczakMaciej Wiznerowicz
May 28, 2015·Cell Division·Maybelline Giam, Giulia Rancati
May 7, 2016·Cell Reports·Marios GiannakisLevi A Garraway

❮ Previous
Next ❯

Citations

Dec 2, 2020·Nature Reviews. Genetics·Erez PersiEugene V Koonin
Apr 4, 2021·International Journal of Molecular Sciences·Noam AuslanderEugene V Koonin
Apr 7, 2021·Seminars in Cell & Developmental Biology·Zuzana Storchova
Aug 12, 2021·Nature Reviews. Cancer·Roman M ChabanonSophie Postel-Vinay

❮ Previous
Next ❯

Methods Mentioned

BETA
chromosomal aberrations

Software Mentioned

UCEC Xena browser
sim
PolyPhen

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Related Papers

Frontiers in Oncology
Samuel F Bakhoum, Charles Swanton
Cellular Oncology : the Official Journal of the International Society for Cellular Oncology
Beatriz Carvalho
Seminars in Cell & Developmental Biology
Marco MilánMariana Muzzopappa
© 2021 Meta ULC. All rights reserved