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mutational signatures

Sunday 10 November 2019


Examples : ultraviolet mutational signature

Definition : Mutational signatures are characteristic combinations of mutation types arising from specific mutagenesis processes such as DNA replication infidelity, exogenous and endogenous genotoxins exposures, defective DNA repair pathways and DNA enzymatic editing.

Deciphering mutational signatures in cancer provides insight into the biological mechanisms involved in carcinogenesis and normal somatic mutagenesis.

Mutational signatures have shown their applicability in cancer treatment and cancer prevention.

Advances in the fields of oncogenomics have enabled the development and use of molecularly targeted therapy, but such therapies historically focused on inhibition of oncogenic drivers (e.g. EGFR gain-of-function mutation and EGFR inhibitor treatment in colorectal cancer).

More recently, mutational signatures profiling has proven successful in guiding oncological management and use of targeted therapies (e.g. immunotherapy in mismatch repair deficient of diverse cancer types, platinum and PARP inhibitor to exploit synthetic lethality in homologous recombination deficient breast cancer - HRD breast cancer).