Molecular Screening in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: Anaplastic Lymphoma Kinase Analysis, Next-Generation Sequencing Fusion Gene Detection, and T-Cell Receptor Immunoprofiling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43926585" target="_blank" >RIV/00064173:_____/24:43926585 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00135937 RIV/00216208:11120/24:43926585 RIV/00216208:11130/24:10474413 RIV/65269705:_____/24:00079661 a 3 dalších

Výsledek na webu

<a href="https://doi.org/10.1016/j.modpat.2024.100428" target="_blank" >https://doi.org/10.1016/j.modpat.2024.100428</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.modpat.2024.100428" target="_blank" >10.1016/j.modpat.2024.100428</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular Screening in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: Anaplastic Lymphoma Kinase Analysis, Next-Generation Sequencing Fusion Gene Detection, and T-Cell Receptor Immunoprofiling

Popis výsledku v původním jazyce

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) originates from the T-lineage and is marked by rearrangements of the ALK gene. Over ten fusion partners with the ALK gene are known, with the most common being the t(2;5)(p23;q35) translocation resulting in the NPM1::ALK fusion. In 10-20% of ALK+ ALCL cases, the ALK gene fuses with various other partners. Modern molecular techniques, especially next-generation sequencing (NGS), have eased the identification of ALK gene fusion partners and have allowed in-depth characterization of the TCR repertoire. We devised a quantitative RT-qPCR to measure the expression of the translocated portion of the ALK gene. Fusion partners for the ALK gene were analyzed using Rapid Amplification of 5&apos;cDNA (RACE) or NGS. T-cell Receptor (TCR) immunoprofiling was performed by amplicon NGS. We studied 96 ALK+ ALCL patients. NPM1::ALK fusion gene was observed in 71 patients, ATIC::ALK in 9, and TPM3::ALK in 3. CLTC::ALK, MYH9::ALK, and RNF213::ALK fusions were identified in 2 patients each. We also discovered the TPM4::ALK and SATB1::ALK fusion genes, plus two previously unidentified ALK+ ALCL fusions: SQSTM1::ALK and CAPRIN1::ALK. High expression of the translocated ALK gene segment was observed in all 93 analyzed samples. TCR testing was conducted on 23 patients with available DNA. In 18 (78%), we discerned at least one (ranging from 1-4) clonal TCR rearrangement. In 59% of patients, clonal TCRB junctions corresponded with sequences previously observed in both healthy donors and under various pathological conditions. RT-qPCR detection of ALK expression is a fast and reliable method for both diagnosing and monitoring treatment response in ALK+ ALCL patients, irrespective of the ALK gene translocation. NGS reveals new ALK translocation partners. Both the malignant and reactive TCR repertoires in ALK+ ALCL patients are unique and do not consistently occur among different patients.

Název v anglickém jazyce

Molecular Screening in Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma: Anaplastic Lymphoma Kinase Analysis, Next-Generation Sequencing Fusion Gene Detection, and T-Cell Receptor Immunoprofiling

Popis výsledku anglicky

Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) originates from the T-lineage and is marked by rearrangements of the ALK gene. Over ten fusion partners with the ALK gene are known, with the most common being the t(2;5)(p23;q35) translocation resulting in the NPM1::ALK fusion. In 10-20% of ALK+ ALCL cases, the ALK gene fuses with various other partners. Modern molecular techniques, especially next-generation sequencing (NGS), have eased the identification of ALK gene fusion partners and have allowed in-depth characterization of the TCR repertoire. We devised a quantitative RT-qPCR to measure the expression of the translocated portion of the ALK gene. Fusion partners for the ALK gene were analyzed using Rapid Amplification of 5&apos;cDNA (RACE) or NGS. T-cell Receptor (TCR) immunoprofiling was performed by amplicon NGS. We studied 96 ALK+ ALCL patients. NPM1::ALK fusion gene was observed in 71 patients, ATIC::ALK in 9, and TPM3::ALK in 3. CLTC::ALK, MYH9::ALK, and RNF213::ALK fusions were identified in 2 patients each. We also discovered the TPM4::ALK and SATB1::ALK fusion genes, plus two previously unidentified ALK+ ALCL fusions: SQSTM1::ALK and CAPRIN1::ALK. High expression of the translocated ALK gene segment was observed in all 93 analyzed samples. TCR testing was conducted on 23 patients with available DNA. In 18 (78%), we discerned at least one (ranging from 1-4) clonal TCR rearrangement. In 59% of patients, clonal TCRB junctions corresponded with sequences previously observed in both healthy donors and under various pathological conditions. RT-qPCR detection of ALK expression is a fast and reliable method for both diagnosing and monitoring treatment response in ALK+ ALCL patients, irrespective of the ALK gene translocation. NGS reveals new ALK translocation partners. Both the malignant and reactive TCR repertoires in ALK+ ALCL patients are unique and do not consistently occur among different patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Modern Pathology

ISSN

0893-3952

e-ISSN

1530-0285

Svazek periodika

37

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

100428

Kód UT WoS článku

001185168200001

EID výsledku v databázi Scopus

2-s2.0-85185557554