Rare Germline ATM Variants Influence the Development of Chronic Lymphocytic Leukemia

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Rare Germline ATM Variants Influence the Development of Chronic Lymphocytic Leukemia

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Rare Germline ATM Variants Influence the Development of Chronic Lymphocytic Leukemia

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

JOURNAL OF CLINICAL ONCOLOGY

ISSN

0732-183X

e-ISSN

1527-7755

Svazek periodika

41

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

1116-1128

Kód UT WoS článku

000946950600022

EID výsledku v databázi Scopus

2-s2.0-85147720497