Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines

摘要

Tumors are characterized by variable numbers of somatic variants that have accumulated during the life history of the cancer cell as a result of abnormal DNA replication and/or DNA repair processes. The classification of such variants into six types based on the nucleotide change was used in the past to differentiate the crude mutation pattern of different cancers.~(1) Recently, the 5′- and 3′-context of each substitution was included in such analyses, expanding the combinations to 96 possible mutation types. This trinucleotide mutational model represents the combined effect of several mutational signatures, and has enough resolution to allow deconvolution of the underlying mutational processes through the non-negative matrix factorization (NNMF) algorithm.~(2) To date, more than 30 distinct signatures have been identified, opening the field to the investigation of the biological processes responsible for shaping the genome of cancer, and allowing a deeper understanding of their relative contribution in different cancer types.~(2, 3).