Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair

Nature Biotechnology
Paz PolakShamil R Sunyaev

Abstract

Carcinogenesis and neoplastic progression are mediated by the accumulation of somatic mutations. Here we report that the local density of somatic mutations in cancer genomes is highly reduced specifically in accessible regulatory DNA defined by DNase I hypersensitive sites. This reduction is independent of any known factors influencing somatic mutation density and is observed in diverse cancer types, suggesting a general mechanism. By analyzing individual cancer genomes, we show that the reduced local mutation density within regulatory DNA is linked to intact global genome repair machinery, with nearly complete abrogation of the hypomutation phenomenon in individual cancers that possess mutations in components of the nucleotide excision repair system. Together, our results connect chromatin structure, gene regulation and cancer-associated somatic mutation.

References

Apr 11, 1975·Science·M C King, A C Wilson
Jan 1, 1988·Annual Review of Biochemistry·D S Gross, W T Garrard
Sep 1, 1997·Molecular and Cellular Biology·J LegaultM E Mirault
Feb 18, 1998·Biochimie·P M Girard, S Boiteux
Dec 4, 2003·Mutation Research·Philip C HanawaltDaniel R Lloyd
Jan 13, 2006·The EMBO Journal·Jean-Philippe Lainé, Jean-Marc Egly
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak
Mar 17, 2009·Nature Genetics·John A StamatoyannopoulosShamil R Sunyaev
Dec 8, 2009·Proceedings of the National Academy of Sciences of the United States of America·R Scott HansenJohn A Stamatoyannopoulos
Dec 18, 2009·Nature·Erin D PleasanceMichael R Stratton
Dec 18, 2009·Nature·Erin D PleasancePeter J Campbell
Sep 18, 2010·Nature Reviews. Genetics·Matthew MeyersonGad Getz
Dec 7, 2010·DNA Repair·Zoraya Palomera-Sanchez, Mario Zurita
Jan 25, 2011·Nature Reviews. Cancer·Sabine S LangeRichard D Wood
Mar 25, 2011·Nature·Michael A ChapmanTodd R Golub
Jul 13, 2011·Nature Reviews. Genetics·Oliver BellDirk Schübeler
Sep 29, 2011·Human Mutation·Alan HodgkinsonAdam Eyre-Walker
Oct 14, 2011·Nature·Kerstin Lindblad-TohManolis Kellis
Nov 15, 2011·Nucleic Acids Research·Minoru KanehisaMao Tanabe
May 12, 2012·Bioinformatics·Shane NephJohn A Stamatoyannopoulos
May 23, 2012·Cell·Serena Nik-ZainalUNKNOWN Breast Cancer Working Group of the International Cancer Genome Consortium
May 25, 2012·Nature·Michael F BergerLevi A Garraway
Jun 30, 2012·Nucleic Acids Research·Nami HarutaTakashi Hishida
Aug 23, 2012·PLoS Genetics·Stephen C J ParkerElliott H Margulies
Sep 8, 2012·Nature·Robert E ThurmanJohn A Stamatoyannopoulos
Sep 8, 2012·Nature·Shane NephJohn A Stamatoyannopoulos
Jan 26, 2013·Science·Franklin W HuangLevi A Garraway
Feb 8, 2013·Nature·Michael B BurnsReuben S Harris
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz

❮ Previous
Next ❯

Citations

Oct 30, 2014·Nature Communications·Ghislaine SceloG Mark Lathrop
May 20, 2015·Nature Genetics·Laurent C FrancioliShamil R Sunyaev
Feb 26, 2016·Annual Review of Pathology·June-Koo LeePeter J Park
Jul 2, 2016·Nature Reviews. Cancer·Inderpreet Sur, Jussi Taipale
Mar 24, 2017·PLoS Computational Biology·Kiwon JangJung Kyoon Choi
Feb 13, 2016·Cancer Cell International·Chuance DuJia Li
Mar 30, 2018·Chromosoma·Anna Fortuny, Sophie E Polo
Nov 9, 2017·Genome Biology·Laurence D Hurst, Nizar N Batada
Jun 14, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jinchuan HuAziz Sancar
Nov 7, 2017·Nature Genetics·Joan FrigolaNúria López-Bigas
Aug 29, 2018·Environmental and Molecular Mutagenesis·Natalie Saini, Dmitry A Gordenin
Feb 26, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Steven A RobertsJohn J Wyrick
Jan 9, 2015·Nature Reviews. Cancer·Steven A Roberts, Dmitry A Gordenin
Apr 15, 2016·Nature·Radhakrishnan SabarinathanNúria López-Bigas
Apr 15, 2016·Nature·Ekta Khurana
Nov 18, 2014·Current Opinion in Oncology·Gerd P Pfeifer
Sep 12, 2015·Oncotarget·Rebecca C PoulosJason W H Wong
Oct 8, 2016·Photochemistry and Photobiology·Peng MaoMichael J Smerdon
Sep 7, 2017·Nature Communications·Matteo D AntonioKelly A Frazer
Nov 30, 2018·PLoS Genetics·Alexander J BrownSteven A Roberts
Sep 18, 2015·Molecular Biology and Evolution·Vladimir B SeplyarskiyRuslan A Soldatov
Mar 24, 2016·Cellular Oncology (Dordrecht)·Angelo Ferraro
Feb 6, 2020·Nature Genetics·Felix DietleinShamil R Sunyaev
Feb 13, 2020·Nature Communications·Tunç MorovaNathan A Lack
Jul 28, 2016·Proceedings of the National Academy of Sciences of the United States of America·Peng MaoJohn J Wyrick
Jul 13, 2017·International Journal of Molecular Sciences·Nidhi NairClaus Storgaard Sørensen
Dec 22, 2017·NPJ Genomic Medicine·Kyungsik HaHwajin Lee
Apr 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sheera AdarAziz Sancar
Mar 23, 2017·Nucleosides, Nucleotides & Nucleic Acids·Senol DoganAmina Kurtovic-Kozaric
May 4, 2017·British Journal of Cancer·Kathryn Hughes BarrySonja I Berndt
Nov 14, 2018·Nature Reviews. Cancer·Siqi LiChristopher M Counter
Aug 12, 2020·Nature Reviews. Cancer·Francisco Martínez-JiménezNuria Lopez-Bigas
Sep 16, 2018·Nature Communications·Jedidiah CarlsonUNKNOWN BRIDGES Consortium

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE29692
GSE18927

Methods Mentioned

BETA
glycosylases
deamination

Software Mentioned

BOWTIE
R
MuTect
BEDOPS
UCSC genome browser

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved