Mutational Landscape Analysis in Systemic Anaplastic Large Cell Lymphoma Identifies Novel Prognostic Markers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F20%3A00073415" target="_blank" >RIV/65269705:_____/20:00073415 - isvavai.cz</a>

Result on the web

<a href="https://www.ceitec.eu/abstract-book-final-docx-pdf/f36324" target="_blank" >https://www.ceitec.eu/abstract-book-final-docx-pdf/f36324</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Mutational Landscape Analysis in Systemic Anaplastic Large Cell Lymphoma Identifies Novel Prognostic Markers

Original language description

Systemic Anaplastic Large Cell Lymphoma comprises two different entities of T-cell non-Hodgkin lymphomas: ALK-positive ALCL characterized by the presence of ALK-translocation, and ALK-negative ALCL, lacking the latter. Both share pathologic features, such as lymphoid cells called &apos;hallmark cells&apos; and the expression of CD30. ALK-positive ALCL shows a better prognosis compared with ALK-negative ALCL, with a 5-years overall survival of 70-80% and 15-45% respectively. Although more than 25% of ALK-positive ALCL patients show relapse. Systemic ALCL is a genetically heterogenous disease whose genomic characterisation has been improved through the implementation of highthroughput technologies. Despite this, the prognostic value of somatic mutations has been poorly described. Using targeted DNA sequencing, we investigated the whole coding region of 275 genes in a retrospective cohort of 82 systemic ALCL patients (47 ALK-positive and 35 ALK-negative), with the aim to improve risk stratification and predict disease outcome. We showed that STAT3 mutations associate with a shorter overall survival in ALK-negative ALCL patients. In addition, we identified TP53 as the most frequently mutated gene in systemic ALCL (5/47 ALK-positive and 8/35 ALK-negative). Moreover, we also showed association between TP53 mutations and shorter progression free survival and the comparison of samples at diagnosis and relapse revealed that clones harbouring aberrations in the TP53 may have a role in disease progression. Altogether, this study provides information about the genetic landscape in systemic ALCL across 275 genes. We identified novel diagnostic and prognostic biomarkers, showing the relationship between mutated genes and outcome. For the first time we have shown a correlation between mutated STAT3 and TP53 with poor prognosis, highlighting the need to investigate the mutational status of those genes at the diagnosis.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10606 - Microbiology

Project

<a href="/en/project/LM2015091" target="_blank" >LM2015091: National Center for Medical Genomic</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

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