Detailed Information on Publication Record
2015
Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia
MALČÍKOVÁ, Jitka, Kateřina STAŇO KOZUBÍK, Boris TICHÝ, Barbara KANTOROVÁ, Šárka PAVLOVÁ et. al.Basic information
Original name
Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia
Authors
MALČÍKOVÁ, Jitka (203 Czech Republic, belonging to the institution), Kateřina STAŇO KOZUBÍK (203 Czech Republic, belonging to the institution), Boris TICHÝ (203 Czech Republic, belonging to the institution), Barbara KANTOROVÁ (203 Czech Republic, belonging to the institution), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Jana ŠMARDOVÁ (203 Czech Republic, belonging to the institution), Filip PARDY (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), Marek MRÁZ (203 Czech Republic, belonging to the institution), Karla PLEVOVÁ (203 Czech Republic, belonging to the institution), Eva DIVÍŠKOVÁ (203 Czech Republic, belonging to the institution), Alexandra OLTOVÁ (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Martin TRBUŠEK (203 Czech Republic, guarantor, belonging to the institution)
Edition
Leukemia, London, NATURE PUBLISHING GROUP, 2015, 0887-6924
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
30200 3.2 Clinical medicine
Country of publisher
United Kingdom of Great Britain and Northern Ireland
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 12.104
RIV identification code
RIV/00216224:14740/15:00082241
Organization unit
Central European Institute of Technology
UT WoS
000352586700015
Keywords in English
LRF CLL4 TRIAL; TERM-FOLLOW-UP; GENOMIC ABERRATIONS; SURVIVAL; FLUDARABINE; P53; CYCLOPHOSPHAMIDE; INACTIVATION; DYSFUNCTION; RESISTANCE
Tags
International impact, Reviewed
Změněno: 29/4/2016 12:44, Mgr. Eva Špillingová
Abstract
V originále
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.
Links
| ED1.1.00/02.0068, research and development project |
| ||
| MUNI/A/0830/2013, interní kód MU |
| ||
| NT13493, research and development project |
| ||
| NT13519, research and development project |
| ||
| 4SGA8684, interní kód MU |
| ||
| 7E13008, research and development project |
|