| TRBUŠEK, Martin, Jana ŠMARDOVÁ, Jitka MALČÍKOVÁ, Ludmila ŠEBEJOVÁ, Petr DOBEŠ, Miluše SVITÁKOVÁ, Vladimíra VRANOVÁ, Marek MRÁZ, Hana SKUHROVÁ FRANCOVÁ, Michael DOUBEK, Yvona BRYCHTOVÁ, Petr KUGLÍK, Šárka POSPÍŠILOVÁ and Jiří MAYER. Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia. Journal of Clinical Oncology. USA: American Society of Clinical Oncology, 2011, vol. 29, No 19, p. 2703-2708. ISSN 0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2011.34.7872. |
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@article{945653,
author = {Trbušek, Martin and Šmardová, Jana and Malčíková, Jitka and Šebejová, Ludmila and Dobeš, Petr and Svitáková, Miluše and Vranová, Vladimíra and Mráz, Marek and Skuhrová Francová, Hana and Doubek, Michael and Brychtová, Yvona and Kuglík, Petr and Pospíšilová, Šárka and Mayer, Jiří},
article_location = {USA},
article_number = {19},
doi = {http://dx.doi.org/10.1200/JCO.2011.34.7872},
keywords = {CLL; TP53; DNA-binding motifs; survival},
language = {eng},
issn = {0732-183X},
journal = {Journal of Clinical Oncology},
title = {Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia},
url = {http://jco.ascopubs.org/content/29/19/2703},
volume = {29},
year = {2011}
}
TY - JOUR
ID - 945653
AU - Trbušek, Martin - Šmardová, Jana - Malčíková, Jitka - Šebejová, Ludmila - Dobeš, Petr - Svitáková, Miluše - Vranová, Vladimíra - Mráz, Marek - Skuhrová Francová, Hana - Doubek, Michael - Brychtová, Yvona - Kuglík, Petr - Pospíšilová, Šárka - Mayer, Jiří
PY - 2011
TI - Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia
JF - Journal of Clinical Oncology
VL - 29
IS - 19
SP - 2703-2708
EP - 2703-2708
PB - American Society of Clinical Oncology
SN - 0732183X
KW - CLL
KW - TP53
KW - DNA-binding motifs
KW - survival
UR - http://jco.ascopubs.org/content/29/19/2703
L2 - http://jco.ascopubs.org/content/29/19/2703
N2 - 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.
ER -
TRBUŠEK, Martin, Jana ŠMARDOVÁ, Jitka MALČÍKOVÁ, Ludmila ŠEBEJOVÁ, Petr DOBEŠ, Miluše SVITÁKOVÁ, Vladimíra VRANOVÁ, Marek MRÁZ, Hana SKUHROVÁ FRANCOVÁ, Michael DOUBEK, Yvona BRYCHTOVÁ, Petr KUGLÍK, Šárka POSPÍŠILOVÁ and Jiří MAYER. Missense mutations located in structural p53 DNA-binding motifs are associated with extremely poor survival in Chronic lymphocytic leukemia. \textit{Journal of Clinical Oncology}. USA: American Society of Clinical Oncology, 2011, vol.~29, No~19, p.~2703-2708. ISSN~0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2011.34.7872.
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