Somatic mutation patterns in non-lymphoid cancers resemble the strand biased somatic hypermutation spectra of antibody genes

Steele, E.J. and Lindley, R.A. (2010) Somatic mutation patterns in non-lymphoid cancers resemble the strand biased somatic hypermutation spectra of antibody genes. DNA Repair, 9 (6). pp. 600-603.

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Abstract

It has been long accepted that many types of B cell cancer (lymphomas, myelomas, plasmacytomas, etc.) are derived from the antigen-stimulated B cell Germinal Center (GC) reaction [1], [2], [3] and [4], i.e. they are aberrant products of the somatic hypermutation mechanism normally targeting rearranged immunoglobulin (Ig) variable genes (so-called V[D]J regions). Here we provide evidence that the somatic mutation patterns of some well-characterised cancer genomes [5] such as lung carcinomas, breast carcinomas and squamous cell carcinomas, strongly resemble in toto or in part the spectrum of somatic point mutations observed in normal physiological somatic hypermutation (SHM) in antibody variable genes [6]. This implies that whilst SHM itself is a tightly regulated and beneficial mutational process for B lymphocytes of the immune system, aberrant mutations (or “crises”) or inadvertent activation of this complex activation-induced cytidine deaminase (AID)-dependent mechanism in a range of somatic tissue types could result, as often speculated [7], in cancer.