Identification of somatic hypermutations in the TP53 gene in B-cell chronic lymphocytic leukemia

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Authors	MALČÍKOVÁ Jitka ŠMARDOVÁ Jana PEKOVÁ Soňa ČEJKOVÁ Soňa KOTAŠKOVÁ Jana TICHÝ Boris FRANCOVÁ Hana DOUBEK Michael BRYCHTOVÁ Yvona JANEK Daniel POSPÍŠILOVÁ Šárka MAYER Jiří DVOŘÁKOVÁ Dana TRBUŠEK Martin
Year of publication	2008
Type	Article in Periodical
Magazine / Source	Molecular Immunology
MU Faculty or unit	Faculty of Science
Citation
Field	Oncology and hematology
Keywords	B cell chronic lymphocytic leukemia; TP53; FASAY; Somatic hypermutation; Activation induced cytidine deaminase
Description	B-cell chronic lymphocytic leukemia is a malignant disease of elderly individuals with highly variable clinical course. Aberrations of TP53 gene together with mutational status of immunoglobulin heavy chain variable region (IgVH) are the most important prognostic factors. Here we report identification of two patients harbouring mutational mosaic of TP53 gene in their leukemic cells using FASAY methodology. On the basis of nucleotide and sequence targeting of the mutations, we can hypothesize, that the IgVH-directed hypermutation machinery is most likely responsible for these multiple TP53 mutations. This process is initiated by activation-induced cytidine deaminase, and in the case of deregulation can be targeted outside the IgVH locus resulting in tumorigenesis. This is the fist report of such TP53 mosaic in B-CLL patients.