Detailed Information on Publication Record
2011
Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia
TRBUŠEK, Martin, Jana ŠMARDOVÁ, Jitka MALČÍKOVÁ, Ludmila ŠEBEJOVÁ, Petr DOBEŠ et. al.Basic information
Original name
Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia
Name in Czech
Missence mutace lokalizovane ve strukturnich DNAvazebnych motivech p53 jsou asociovany s extremne spatnym prezitim u chronicke lymfocytarni leukemie
Authors
TRBUŠEK, Martin (203 Czech Republic, guarantor, belonging to the institution), Jana ŠMARDOVÁ (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution), Ludmila ŠEBEJOVÁ (203 Czech Republic, belonging to the institution), Petr DOBEŠ (203 Czech Republic, belonging to the institution), Miluše SVITÁKOVÁ (203 Czech Republic, belonging to the institution), Vladimíra VRANOVÁ (703 Slovakia, belonging to the institution), Marek MRÁZ (203 Czech Republic, belonging to the institution), Hana SKUHROVÁ FRANCOVÁ (203 Czech Republic, belonging to the institution), Michael DOUBEK (203 Czech Republic, belonging to the institution), Yvona BRYCHTOVÁ (203 Czech Republic, belonging to the institution), Petr KUGLÍK (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Jiří MAYER (203 Czech Republic, belonging to the institution)
Edition
Journal of Clinical Oncology, USA, American Society of Clinical Oncology, 2011, 0732-183X
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30200 3.2 Clinical medicine
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 18.372
RIV identification code
RIV/00216224:14740/11:00052704
Organization unit
Central European Institute of Technology
UT WoS
000292210500024
Keywords in English
CLL; TP53; DNA-binding motifs; survival
Tags
International impact
Změněno: 7/4/2012 06:28, Olga Křížová
V originále
Purpose There is a distinct connection between TP53 defects and poor prognosis in chronic lymphocytic leukemia (CLL). It remains unclear whether patients harboring TP53 mutations represent a homogenous prognostic group. Patients and Methods We evaluated the survival of patients with CLL and p53 defects identified at our institution by p53 yeast functional assay and complementary interphase fluorescence in situ hybridization analysis detecting del(17p) from 2003 to 2010. Results A defect of the TP53 gene was identified in 100 of 550 patients. p53 mutations were strongly associated with the deletion of 17p and the unmutated IgVH locus (both P .001). Survival assessed from the time of abnormality detection was significantly reduced in patients with both missense (P .001) and nonmissense p53 mutations (P .004). In addition, patients harboring missense mutation located in p53 DNA-binding motifs (DBMs), structurally well-defined parts of the DNA-binding domain, manifested a clearly shorter median survival (12 months) compared with patients having missense mutations outside DBMs (41 months; P .002) or nonmissense alterations (36 months; P .005). The difference in survival was similar in the analysis limited to patients harboring mutation accompanied by del(17p) and was also confirmed in a subgroup harboring TP53 defect at diagnosis. The patients with p53 DBMs mutation (at diagnosis) also manifested a short median time to first therapy (TTFT; 1 month). Conclusion The substantially worse survival and the short TTFT suggest a strong mutated p53 gain-of-function phenotype in patients with CLL with DBMs mutations. The impact of p53 DBMs mutations on prognosis and response to therapy should be analyzed in investigative clinical trials.
In Czech
Existuje prime spojeni mezi defekty v genu TP53 a spatnou prognozou u chronicke lymfocytarni leukemie. Zustava ale nejasne, zda pacienti, kteri maji mutace v genu TP53 reprezentuji homogenni prognostickou skupinu. Hodnotili jsme preziti pacientu s CLL a defekty v p53 identifikovanych v nasi laboratori pomoci kvasinkove funkcni analyzy p53 a komplementarne interfazni fluorescencni in situ hybridizacni analyzou detekujici del(17p) od roku 2003 do roku 2010. Defekty v genu TP53 byly identifikovany ve 100 z 550 pacientu. Mutace v p53 byly silne asociovany s deleci 17p a nemutovanym lokusem IgVH (oba P .001). Preziti pacientu stanovene od data detekce abnormality bylo signifikantne snizene u pacientu s missence (P .001) i non-missence p53 mutacemi (P= .004).
Links
| MSM0021622430, plan (intention) |
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| NS10448, research and development project |
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