ATM and TP53 mutations show mutual exclusivity but distinct
clinical impact in mantle cell lymphoma patients

J 2019

ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients

MAREČKOVÁ, Andrea, Jitka MALČÍKOVÁ, Nikola TOM, Karol PÁL, Lenka RADOVÁ et. al.

Basic information

Original name

ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients

Authors

MAREČKOVÁ, Andrea (203 Czech Republic, belonging to the institution), Jitka MALČÍKOVÁ (203 Czech Republic, belonging to the institution), Nikola TOM (203 Czech Republic, belonging to the institution), Karol PÁL (703 Slovakia, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), David ŠÁLEK (203 Czech Republic, belonging to the institution), Andrea JANÍKOVÁ (203 Czech Republic, belonging to the institution), Mojmír MOULIS (203 Czech Republic, belonging to the institution), Jana ŠMARDOVÁ (203 Czech Republic, belonging to the institution), Leoš KŘEN (203 Czech Republic, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Martin TRBUŠEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

LEUKEMIA & LYMPHOMA, LONDON, INFORMA HEALTHCARE, 2019, 1042-8194

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 2.969

RIV identification code

RIV/00216224:14110/19:00108352

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1080/10428194.2018.1542144

UT WoS

000472447600009

Keywords in English

Mantle cell lymphoma; ATM; TP53; p21; SOX11; survival

Abstract

V originále

Mantle cell lymphoma (MCL) is characterized by the hallmark t(11;14)(q13;q32) translocation, leading to cyclin D1 over-expression. Additionally, disrupting the DNA damage response pathway through ATM or TP53 defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of ATM and TP53 mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated ATM and TP53 alleles were found in 51% (37/72) and 22% (16/72) of the cases examined, respectively, with only three patients harboring mutations in both genes. Only a mutated TP53 gene was associated with the significantly reduced PFS and OS and the same output was observed when ATM and TP53 defective groups included also sole deletions 11q and 17p, respectively. Determining the exact ATM/p53 pathway dysfunction may influence the selection of MCL patients for innovative therapies based on the targeted inhibition of selected proteins.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

TE02000058, research and development project

Name: Centrum kompetence pro molekulární diagnostiku a personalizovanou medicínu (Acronym: MOLDIMED)

Investor: Technology Agency of the Czech Republic

90091, large research infrastructures

Name: NCMG

Citovat

MAREČKOVÁ, Andrea, Jitka MALČÍKOVÁ, Nikola TOM, Karol PÁL, Lenka RADOVÁ, David ŠÁLEK, Andrea JANÍKOVÁ, Mojmír MOULIS, Jana ŠMARDOVÁ, Leoš KŘEN, Jiří MAYER and Martin TRBUŠEK. ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients. LEUKEMIA & LYMPHOMA. LONDON: INFORMA HEALTHCARE, 2019, vol. 60, No 6, p. 1420-1428. ISSN 1042-8194. Available from: https://dx.doi.org/10.1080/10428194.2018.1542144.

@article{1545496,
   author = {Marečková, Andrea and Malčíková, Jitka and Tom, Nikola and Pál, Karol and Radová, Lenka and Šálek, David and Janíková, Andrea and Moulis, Mojmír and Šmardová, Jana and Křen, Leoš and Mayer, Jiří and Trbušek, Martin},
   article_location = {LONDON},
   article_number = {6},
   doi = {http://dx.doi.org/10.1080/10428194.2018.1542144},
   keywords = {Mantle cell lymphoma; ATM; TP53; p21; SOX11; survival},
   language = {eng},
   issn = {1042-8194},
   journal = {LEUKEMIA & LYMPHOMA},
   title = {ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients},
   url = {http://dx.doi.org/10.1080/10428194.2018.1542144},
   volume = {60},
   year = {2019}
}

TY  - JOUR
ID  - 1545496
AU  - Marečková, Andrea - Malčíková, Jitka - Tom, Nikola - Pál, Karol - Radová, Lenka - Šálek, David - Janíková, Andrea - Moulis, Mojmír - Šmardová, Jana - Křen, Leoš - Mayer, Jiří - Trbušek, Martin
PY  - 2019
TI  - ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients
JF  - LEUKEMIA & LYMPHOMA
VL  - 60
IS  - 6
SP  - 1420-1428
EP  - 1420-1428
PB  - INFORMA HEALTHCARE
SN  - 10428194
KW  - Mantle cell lymphoma
KW  - ATM
KW  - TP53
KW  - p21
KW  - SOX11
KW  - survival
UR  - http://dx.doi.org/10.1080/10428194.2018.1542144
L2  - http://dx.doi.org/10.1080/10428194.2018.1542144
N2  - Mantle cell lymphoma (MCL) is characterized by the hallmark t(11;14)(q13;q32) translocation, leading to cyclin D1 over-expression. Additionally, disrupting the DNA damage response pathway through ATM or TP53 defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of ATM and TP53 mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated ATM and TP53 alleles were found in 51% (37/72) and 22% (16/72) of the cases examined, respectively, with only three patients harboring mutations in both genes. Only a mutated TP53 gene was associated with the significantly reduced PFS and OS and the same output was observed when ATM and TP53 defective groups included also sole deletions 11q and 17p, respectively. Determining the exact ATM/p53 pathway dysfunction may influence the selection of MCL patients for innovative therapies based on the targeted inhibition of selected proteins.
ER  -

MAREČKOVÁ, Andrea, Jitka MALČÍKOVÁ, Nikola TOM, Karol PÁL, Lenka RADOVÁ, David ŠÁLEK, Andrea JANÍKOVÁ, Mojmír MOULIS, Jana ŠMARDOVÁ, Leoš KŘEN, Jiří MAYER and Martin TRBUŠEK. ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients. \textit{LEUKEMIA \&{}amp; LYMPHOMA}. LONDON: INFORMA HEALTHCARE, 2019, vol.~60, No~6, p.~1420-1428. ISSN~1042-8194. Available from: https://dx.doi.org/10.1080/10428194.2018.1542144.

Detailed Information on Publication Record