TY - JOUR
T1 - Signatures of mutational processes in human cancer
AU - Alexandrov, Ludmil B.
AU - Nik-Zainal, Serena
AU - Wedge, David C.
AU - Aparicio, Samuel A. J. R.
AU - Behjati, Sam
AU - Biankin, Andrew V.
AU - Bignell, Graham R.
AU - Bolli, Niccolo
AU - Borg, Ake
AU - Borresen-Dale, Anne-Lise
AU - Boyault, Sandrine
AU - Burkhardt, Birgit
AU - Butler, Adam P.
AU - Caldas, Carlos
AU - Davies, Helen R.
AU - Desmedt, Christine
AU - Eils, Roland
AU - Eyfjord, Jorunn Erla
AU - Foekens, John A.
AU - Merrett, Neil
PY - 2013
Y1 - 2013
N2 - All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
AB - All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
UR - http://handle.uws.edu.au:8081/1959.7/540434
UR - http://search.proquest.com/docview/1440313159?accountid=36155
M3 - Article
SN - 0028-0836
VL - 500
SP - 415
EP - 421
JO - Nature
JF - Nature
IS - 7463
ER -