Associação Portuguesa de Investigação em Cancro
Discovery of mutational signatures in the 30 more common cancer types
Discovery of mutational signatures in the 30 more common cancer types
An international team of investigators, including Portuguese scientists Carlos Caldas and Samuel Aparício identified, by studying the genome of 7000 patients, more than 20 mutational signatures that lead to the 30 more common cancer types. This study was published in Nature and contains information that will help to understand cancer aetiology and development and also to improve prevention and treatment strategies.
The mutational signatures identified are very heterogeneous and can be restricted to a single tumour type or shared by different neoplasias. They can also relat to various factors, like age, cancer type and exposure to mutagenic agents.
The Consortium responsible for the study involves researchers from 14 countries, has the contribution of two portuguese – Samuel Aparício, from the Cancer Agency of British Columbia, Vancouver, Canada, and Carlos Caldas, from the University of Cambridge, UK, and is leaded by Mike Stratton, director of the Wellcome Trust Sanger Institute, UK.
Authors and affiliations:
Ludmil B. Alexandrov, Serena Nik-Zainal, David C. Wedge, Samuel A. J. R. Aparicio, Sam Behjati, Andrew V. Biankin, Graham R. Bignell, Niccolò Bolli, Ake Borg, Anne-Lise Børresen-Dale, Sandrine Boyault, Birgit Burkhardt, Adam P. Butler, Carlos Caldas, Helen R. Davies, Christine Desmedt, Roland Eils, Jórunn Erla Eyfjörd, John A. Foekens, Mel Greaves, Fumie Hosoda, Barbara Hutter, Tomislav Ilici, Sandrine Imbeaud, Marcin Imielinsk
Cancer Genome Project, Wellcome Trust Sanger Institute, UK
Abstract:
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.
Journal:
Nature
Link:
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12477.html
