The detection of TP53 mutations in chronic lymphocytic leukemia
Authors:
B. Kantorová; J. Pavlíček; R. Plachý; T. Papajík; M. Jarošová
Authors‘ workplace:
Hemato-onkologická klinika FN a LF UP v Olomouci
Published in:
Transfuze Hematol. dnes,16, 2010, No. 2, p. 71-77.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western countries. CLL is a heterogeneous disease characterized by a number of clinical and biological prognostic markers, one of the most important being mutations of the TP53 gene. To study the TP53 gene, we retrospectively investigated 72 patients with CLL using direct sequencing and high-resolution melting curve analysis (hrMCA). We found modifications of the TP53 gene in 46 (64%) patients. We detected 59 modifications of the TP53 gene (exons 2-10) in 45 (62%) patients by direct sequencing. Among these modifications, we identified 23 mutations in 20 (28%) patients. These were substitutions (83% of the mutations) and deletions (17% of the mutations). The substitutions comprised missense (90%), nonsense (5%) and silent mutations (5%). Ninety one percent of the mutations were located in the DNA-binding domain (exons 5-8) of the TP53 gene. We detected 87% of the mutations in patients with high-risk disease. We showed a statistical relationship between mutations in the TP53 gene and chromosome 17p deletion (P < 0.000001). We also observed correlation between mutations in the TP53 gene and Binet stage of CLL (P = 0.027). We found 32 aberrant PCR products of the TP53 gene (exons 5-8) in 26 (36%) patients by hrMCA. The method is more sensitive and faster than direct sequencing. However, our experience suggests that due to problems with standardization, hrMCA is not suitable for routine detection of modifications of the gene TP53 in patients with CLL.
Key words:
gene TP53, chronic lymphocytic leukemia, direct sequencing, high-resolution melting curve analysis
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Haematology Internal medicine Clinical oncologyArticle was published in
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