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

Autor: Yvona Brychtová, Soňa Čejková, Boris Tichy, Jitka Malčíková, Jiří Mayer, Michael Doubek, Jana Šmardová, S. Pekova, Dana Dvorakova, Martin Trbušek, Hana Skuhrová Francová, Šárka Pospíšilová, D. Janek, Jana Kotašková
Rok vydání: 2008
Předmět:
Zdroj: Molecular Immunology. 45:1525-1529
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2007.08.017
Popis: Abnormalities of the TP53 gene are associated with a particularly severe prognosis in patients with B-cell chronic lymphocytic leukemia (B-CLL). This tumor-suppressor is mostly inactivated by the deletion of one and point mutation of the other allele and has not been previously shown to be hypermutated in B-CLL. We identified two patients whose lymphocytes showed repeatedly an extensive proportion of TP53 mutated cells by FASAY analysis (the yeast functional assay) and harbored various TP53 mutations, mostly single-base substitutions, in individual cells. The mutation targeting exhibited characteristic traits of the somatic hypermutation process. In the first patient (harboring the unmutated IgVH locus) a significant bias to point mutations at CG pairs (21/25; P=0.009), their remarkable preference for the RGYW/WRCY motives (28%) and the highest expression of the activation-induced cytidine deaminase (AID) mRNA among the 34 tested B-CLL samples. In the second patient no CG bias was observed but the targeting of point mutations into the RGYW/WRCY motives was even more prominent here (7/16; 44%). Moreover, six out of eight point mutations affecting AT pairs were localized in the WA/TW motives, which are also characteristic for the somatic hypermutations. This patient, who was IgVH-mutated, already did not express any significant amount of the AID transcript. Our findings add a new aspect to the mosaic of the p53 mutability in B-CLL.
Databáze: OpenAIRE
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