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TP 53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia
Author(s) -
Malcikova Jitka,
Pavlova Sarka,
Kozubik Katerina Stano,
Pospisilova Sarka
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22508
Subject(s) - biology , chronic lymphocytic leukemia , leukemia , mutation , genetics , dna sequencing , bioinformatics , gene
ABSTRACT In leukemia, TP 53 mutations are not frequent but clearly associate with impaired survival and therapy response. Here, we describe the biological and clinical consequences of TP 53 dysfunction as well as the methodical aspects of TP 53 analysis in chronic lymphocytic leukemia ( CLL ). In CLL , TP 53 defects are routinely analyzed as part of disease prognostication. Deletions of TP 53 locus (17p) have been uniformly detected using I ‐ FISH for several years. Since monoallelic mutations have also been shown to have negative prognostic impact, it is recommended to examine both TP 53 mutations and deletions. Several methods are used to detect TP 53 mutations, and next‐generation sequencing ( NGS ) is becoming a convenient option for routine analysis. Besides this, ultradeep NGS permits the detection of minor clones carrying TP 53 mutations, even below 1%. The prognostic impact of minor TP 53 ‐defective subclones is currently unknown, nevertheless they unequivocally bear the risk of being selected by therapy. Prospective studies assessing the consequences of carrying such clones are in progress.