title: TP53 mutation analysis in clinical practice: lessons from chronic lymphocytic leukemia.
abstract: In leukemia, TP53 mutations are not frequent but clearly associate with impaired survival and therapy response. Here, we describe the biological and clinical consequences of TP53 dysfunction as well as the methodical aspects of TP53 analysis in chronic lymphocytic leukemia (CLL). In CLL, TP53 defects are routinely analyzed as part of disease prognostication. Deletions of TP53 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 TP53 mutations and deletions. Several methods are used to detect TP53 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 TP53 mutations, even below 1%. The prognostic impact of minor TP53-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.
authors.affiliation: Central European Institute of Technology, Center of Molecular Medicine, and Faculty of Medicine, Department of Internal Medicine - Hematology and Oncology, Masaryk University, Brno, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Malcikova
authors.forename: Sarka
authors.initials: S
authors.lastname: Pavlova
authors.forename: Katerina Stano
authors.initials: KS
authors.lastname: Kozubik
authors.forename: Sarka
authors.initials: S
authors.lastname: Pospisilova
mesh_terms: D004252:DNA Mutational Analysis; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D017384:Sequence Deletion / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: TP53; chronic lymphocytic leukemia; clonal evolution; next generation sequencing; p53