| MALČÍKOVÁ, Jitka, Kateřina STAŇO KOZUBÍK, Boris TICHÝ, Barbara KANTOROVÁ, Šárka PAVLOVÁ, Nikola TOM, Lenka RADOVÁ, Jana ŠMARDOVÁ, Filip PARDY, Michael DOUBEK, Yvona BRYCHTOVÁ, Marek MRÁZ, Karla PLEVOVÁ, Eva DIVÍŠKOVÁ, Alexandra OLTOVÁ, Jiří MAYER, Šárka POSPÍŠILOVÁ a Martin TRBUŠEK. Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia. Leukemia. London: NATURE PUBLISHING GROUP, 2015, roč. 29, č. 4, s. 877-885. ISSN 0887-6924. Dostupné z: https://dx.doi.org/10.1038/leu.2014.297. |
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@article{1216620,
author = {Malčíková, Jitka and Staňo Kozubík, Kateřina and Tichý, Boris and Kantorová, Barbara and Pavlová, Šárka and Tom, Nikola and Radová, Lenka and Šmardová, Jana and Pardy, Filip and Doubek, Michael and Brychtová, Yvona and Mráz, Marek and Plevová, Karla and Divíšková, Eva and Oltová, Alexandra and Mayer, Jiří and Pospíšilová, Šárka and Trbušek, Martin},
article_location = {London},
article_number = {4},
doi = {http://dx.doi.org/10.1038/leu.2014.297},
keywords = {LRF CLL4 TRIAL; TERM-FOLLOW-UP; GENOMIC ABERRATIONS; SURVIVAL; FLUDARABINE; P53; CYCLOPHOSPHAMIDE; INACTIVATION; DYSFUNCTION; RESISTANCE},
language = {eng},
issn = {0887-6924},
journal = {Leukemia},
title = {Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia},
url = {http://www.nature.com/leu/journal/v29/n4/pdf/leu2014297a.pdf},
volume = {29},
year = {2015}
}
TY - JOUR
ID - 1216620
AU - Malčíková, Jitka - Staňo Kozubík, Kateřina - Tichý, Boris - Kantorová, Barbara - Pavlová, Šárka - Tom, Nikola - Radová, Lenka - Šmardová, Jana - Pardy, Filip - Doubek, Michael - Brychtová, Yvona - Mráz, Marek - Plevová, Karla - Divíšková, Eva - Oltová, Alexandra - Mayer, Jiří - Pospíšilová, Šárka - Trbušek, Martin
PY - 2015
TI - Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia
JF - Leukemia
VL - 29
IS - 4
SP - 877-885
EP - 877-885
PB - NATURE PUBLISHING GROUP
SN - 08876924
KW - LRF CLL4 TRIAL
KW - TERM-FOLLOW-UP
KW - GENOMIC ABERRATIONS
KW - SURVIVAL
KW - FLUDARABINE
KW - P53
KW - CYCLOPHOSPHAMIDE
KW - INACTIVATION
KW - DYSFUNCTION
KW - RESISTANCE
UR - http://www.nature.com/leu/journal/v29/n4/pdf/leu2014297a.pdf
L2 - http://www.nature.com/leu/journal/v29/n4/pdf/leu2014297a.pdf
N2 - In chronic lymphocytic leukemia (CLL), the worst prognosis is associated with TP53 defects with the affected patients being potentially directed to alternative treatment. Therapy administration was shown to drive the selection of new TP53 mutations in CLL. Using ultra-deep next-generation sequencing (NGS), we performed a detailed analysis of TP53 mutations' clonal evolution. We retrospectively analyzed samples that were assessed as TP53-wild-type (wt) by FASAY from 20 patients with a new TP53 mutation detected in relapse and 40 patients remaining TP53-wt in relapse. Minor TP53-mutated subclones were disclosed in 18/20 patients experiencing later mutation selection, while only one minor-clone mutation was observed in those patients remaining TP53-wt (n=40). We documented that (i) minor TP53 mutations may be present before therapy and may occur in any relapse; (ii) the majority of TP53-mutated minor clones expand to dominant clone under the selective pressure of chemotherapy, while persistence of minor-clone mutations is rare; (iii) multiple minor-clone TP53 mutations are common and may simultaneously expand. In conclusion, patients with minor-clone TP53 mutations carry a high risk of mutation selection by therapy. Deep sequencing can shift TP53 mutation identification to a period before therapy administration, which might be of particular importance for clinical trials.
ER -
MALČÍKOVÁ, Jitka, Kateřina STAŇO KOZUBÍK, Boris TICHÝ, Barbara KANTOROVÁ, Šárka PAVLOVÁ, Nikola TOM, Lenka RADOVÁ, Jana ŠMARDOVÁ, Filip PARDY, Michael DOUBEK, Yvona BRYCHTOVÁ, Marek MRÁZ, Karla PLEVOVÁ, Eva DIVÍŠKOVÁ, Alexandra OLTOVÁ, Jiří MAYER, Šárka POSPÍŠILOVÁ a Martin TRBUŠEK. Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia. \textit{Leukemia}. London: NATURE PUBLISHING GROUP, 2015, roč.~29, č.~4, s.~877-885. ISSN~0887-6924. Dostupné z: https://dx.doi.org/10.1038/leu.2014.297.
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