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, 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.

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

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30204 Oncology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: 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
• Tags: 14110212, 14110230, CF GEN, podil, rivok
• Tags: International impact, Reviewed

Abstract

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

• LM2015091, research and development project: Name: Národní centrum lékařské genomiky (Acronym: NCLG)

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

• 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