Cancer Institute Seminar Series - Prof Ludmil Alexandrov

Hosted by Dr Nischalan Pillay
 
A light lunch will be served after the seminar. 
 
Cancer is the most common human genetic disease. All cancers are caused by somatic mutations. These mutations may be the consequence of the intrinsic slight infidelity of the DNA replication machinery, exogenous or endogenous mutagen exposures, enzymatic modification of DNA, or defective DNA repair. In some cancer types, a substantial proportion of somatic mutations are known to be generated by exogenous carcinogens, for example, tobacco smoking in lung cancers and ultraviolet light in skin cancers, or by abnormalities of DNA maintenance, for example, defective DNA mismatch repair in some colorectal cancers. Each biological process causing mutations leaves a characteristic imprint on the genome of a cancer cell, termed, mutational signature. In this talk, I will present mutational signatures analyses encompassing 30,874 cancer genomes across 91 distinct types of human cancer revealing more than 60 different signatures of mutational processes. Some signatures 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. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer etiology, prevention and therapy.