Inaktivace p53 a delece ATM v souboru B-CLL pacientů ve vztahu k mutačnímu statusu IgVH a léčbě

Title in English Inactivation of TP53 and ATM in relation to IgVH mutation status and previous treatment
Authors

BUKOVSKÁ Soňa TRBUŠEK Martin MALČÍKOVÁ Jitka ŠMARDOVÁ Jana CHUMCHALOVÁ Jitka SVITÁKOVÁ Miluše MENTZLOVÁ Dita LINKOVÁ Věra KUGLÍK Petr KUHROVÁ Viera FRANCOVÁ Hana DOUBEK Michael BRYCHTOVÁ Yvona MAYER Jiří

Year of publication 2006
Type Article in Periodical
Magazine / Source Chemické listy
MU Faculty or unit

Faculty of Medicine

Citation
Field Oncology and hematology
Keywords B-CLL p53 ATM IgVH previous treatment
Description The p53 abnormalities were reported to be associated with unmutated IgVH subtype and may thus arise as a consequence of its more aggressive behaviour, but some reports point also to potentially damaging chemotherapy including alkylating agents. We analyzed the status of the p53 gene using functional analysis in yeasts (FASAY) supplemented by Western-blotting detection of p53 protein expression and I-FISH detection of p53 deletions (LSI p53 17p13.1). We used PCR and direct sequencing to analyze the IgVH rearrangements and mutation status. Our comprehensive approach for monitoring of p53 abnormalities provided us the overall frequency of inactivation within the expected range (16/168 = 9,5%). 21 cases (18%) manifested mutation in ATM gene IgVH, only onecase show paralel mutation in p53 and ATM. The overall treatment, which included alkylating agents, was markedly more frequent within the subgroup with germ-line IgVH compared to group harboring mutated IgVH. The spectrum of p53 mutations in our population is different from those reported in other studies. The inactivation of the p53 was in our study associated with unmutated IgVH locus and does not seem to be primarily the consequence of previous chemotherapy including alkylating agents.

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