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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

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

30109 - Pathology

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

2024

Confidentiality

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

Name of the periodical

Modern Pathology

ISSN

0893-3952

e-ISSN

1530-0285

Volume of the periodical

37

Issue of the periodical within the volume

3

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

100428

UT code for WoS article

001185168200001

EID of the result in the Scopus database

2-s2.0-85185557554