The International Cancer Genome Consortium compiles the processes which alter DNA and lead to the disease
All cancers are caused by alterations in DNA, acquired over patientsʼ lifetimes, which bear the signatures of the mutational processes that have been operative. They leave a distinctive mutation signature in the genome of each tumour. The somatic mutations known up to now were the ones generated by exposures, for example, tobacco smoking in lung cancers and ultraviolet light in skin cancers, but the mechanisms involved in the development of most tumours remained unknown.
The research has analysed 7,042 genomes of patients who suffer common types of cancers and extracted more than 20 distinct mutational signatures. Moreover, the biological processes associated to the development of most mutational processes have also been identified. Some mutational signatures are present in many cancer types, whereas others are confined to a single cancer type. Interestingly, only two mutational signatures were observed in some tumours, but a maximum of six were identified in liver, uterus and stomach cancers. These differences may likely indicate that some cancers have a more complex repertoire of mutational processes than others.
The contribution of the Spanish research group to the international research is the identification of two mechanisms which cause mutations in Chronic Lymphocytic Leukaemia: one of them is related to age and the other one to DNA repair. To be exact, the research group has studied in detail the mutational signatures of more than 100 genomes of leukaemia patients.
Dr Elías Campo explains that “most mutation signatures explaining gene development and the history of analysed cancers have been identified. We are facing one of the first examples of the new view that massive and coordinated genome sequencing can offer by means of the International Cancer Genome Consortium”. Dr Carlos López Otín remarks that, “thanks to the close collaboration of each international research group, the results obtained are such important. A detailed analysis of the information generated will enable to develop new approaches to study the molecular mechanisms involved in tumours”.
“Mutational processes definition —the coordinators of the project in Spain— is an important step forward in discovering how and why cancer is originated. The compilation of mutational signatures and their consequent perspectives in mutational processes will advance our understanding of cancer aetiology with potential implications for prevention and treatment”.
Reference:
Alexandrov, L. B.; Behjati, S.; Biankin, A. V.; Bignell, G. R.; Bolli, N.; Borg, A.; Campo, E.; López Otín, C.; Nik-Zainal, S.; Stratton, M. R. et al. “Signatures of mutational processes in human cancer”. Nature, August 2013. Doi:10.1038/nature12477
Further information:
Chronic Lymphocytic Leukaemia Genome Project