Rare Germline ATM Variants Influence the Development of Chronic Lymphocytic Leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73614534" target="_blank" >RIV/61989592:15110/23:73614534 - isvavai.cz</a>

Result on the web

<a href="https://ascopubs.org/doi/pdf/10.1200/JCO.22.00269?role=tab" target="_blank" >https://ascopubs.org/doi/pdf/10.1200/JCO.22.00269?role=tab</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/JCO.22.00269" target="_blank" >10.1200/JCO.22.00269</a>

Result language

angličtina

Original language name

Rare Germline ATM Variants Influence the Development of Chronic Lymphocytic Leukemia

Original language description

PURPOSE Germline missense variants of unknown significance in cancer-related genes are increasingly beingidentified with the expanding use of next-generation sequencing. The ataxia telangiectasia–mutated (ATM) geneon chromosome 11 has more than 1,000 germline missense variants of unknown significance and is a tumorsuppressor. We aimed to determine if rare germline ATM variants are more frequent in chronic lymphocyticleukemia (CLL) compared with other hematologic malignancies and if they influence the clinical characteristicsof CLL.METHODS We identified 3,128 patients (including 825 patients with CLL) in our hematologic malignancy clinicwho had received clinical-grade sequencing of the entire coding region of ATM.We ascertained the comparativefrequencies of germline ATM variants in categories of hematologic neoplasms, and, in patients with CLL, wedetermined whether these variants affected CLL-associated characteristics such as somatic 11q deletion.RESULTS Rare germline ATM variants are present in 24% of patients with CLL, significantly greater than that inpatients with other lymphoid malignancies (16% prevalence), myeloid disease (15%), or no hematologicneoplasm (14%). Patients with CLL with germline ATM variants are younger at diagnosis and twice as likely tohave 11q deletion. The ATM variant p.L2307F is present in 3% of patients with CLL, is associated with a threefoldincrease in rates of somatic 11q deletion, and is a hypomorph in cell-based assays.CONCLUSION Germline ATM variants cluster within CLL and affect the phenotype of CLL that develops, implyingthat some of these variants (such as ATM p.L2307F) have functional significance and should not be ignored.Further studies are needed to determine whether these variants affect the response to therapy or account forsome of the inherited risk of CLL.

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

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

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

Name of the periodical

JOURNAL OF CLINICAL ONCOLOGY

ISSN

0732-183X

e-ISSN

1527-7755

Volume of the periodical

41

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

1116-1128

UT code for WoS article

000946950600022

EID of the result in the Scopus database

2-s2.0-85147720497