Fundamental prognostic difference of ATM gene mutation and deletion in newly diagnosed mantle cell lymphoma

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00098892%3A_____%2F25%3A10159453" target="_blank" >RIV/00098892:_____/25:10159453 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/25:10504103 RIV/00064165:_____/25:10504103 RIV/61989592:15110/25:73631976 RIV/61989592:15310/25:73631976

Result on the web

<a href="https://molmed.biomedcentral.com/articles/10.1186/s10020-025-01376-2" target="_blank" >https://molmed.biomedcentral.com/articles/10.1186/s10020-025-01376-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s10020-025-01376-2" target="_blank" >10.1186/s10020-025-01376-2</a>

Result language

angličtina

Original language name

Fundamental prognostic difference of ATM gene mutation and deletion in newly diagnosed mantle cell lymphoma

Original language description

Background: Previous studies have suggested that, after acquisition of t(11;14), mantle cell lymphoma (MCL) pathogenesis may proceed via several different genetic second hits, which may shape different mutational profiles of clinically manifest lymphoma. The most prevalent second hit in MCL includes ATM aberrations, accounting for about half of patients with newly diagnosed MCL. As ATM and TP53 mutations tend to be exclusive in MCL, we retrospectively analyzed the prognostic role of ATM deletions and/or mutations in patients with newly diagnosed MCL, both in the entire cohort and in a subcohort of patients with wild-type TP53. Methods: To investigate deletions and mutations of ATM and TP53 in newly diagnosed MCL, we used fluorescence in situ hybridization and next-generation sequencing. To assess relationships between variables, non-parametric (Spearman) and chi-square tests were used. The Kruskal–Wallis test was used to analyze differences in continuous variables between two groups of patients. For survival analyses, the standard Kaplan–Meier estimator and log-rank test were employed. Univariate and multivariate Cox proportional hazard models were used to examine the prognostic value of various factors on patient survival. Results: We analyzed 187 patients with MCL (a median follow-up of 3.6 years). Eighty-one (43%) and 75 (40%) patients had ATM and TP53 aberrations, respectively. Of note, three (9%) patients with mutated ATM harbored a germline mutation. Patients with TP53 aberration had shorter survival rates. Although ATM deletion did not correlate with progression-free survival (PFS) in the entire cohort, it was associated with shorter PFS (hazard ratio 2.25, p = 0.01) in patients with wild-type TP53. A higher frequency of ATM deletion correlated with shorter PFS. Patients with ATM mutation (and wild-type TP53) had a trend toward better PFS (albeit not statistically significant). Moreover, patients with a higher variant allele frequency of ATM mutation tended to have longer PFS. Conclusions: ATM deletion is an important predictor of prognosis in MCL patients and should be routinely examined, especially in those with wild-type TP53. In contrast, an isolated ATM mutation may predict a better prognosis in the context of standard immunochemotherapy.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Medicine

ISSN

1076-1551

e-ISSN

1528-3658

Volume of the periodical

31

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

306

UT code for WoS article

001586147700002

EID of the result in the Scopus database

2-s2.0-105017762707