Identification of novel chronic lymphocytic leukemia subtypes using pathway mutation scores and consensus clustering

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00071771" target="_blank" >RIV/65269705:_____/19:00071771 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/19:00108577

Result on the web

<a href="https://www.nature.com/articles/s41431-019-0494-2" target="_blank" >https://www.nature.com/articles/s41431-019-0494-2</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Identification of novel chronic lymphocytic leukemia subtypes using pathway mutation scores and consensus clustering

Original language description

Introduction: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with variable clinical course underlain by striking genetic heterogeneity. CLL features a handful of putative driver genes and, more interestingly, a large number of non-recurrently mutated genes with elusive clinical implications. The aim of this study was to unravel the prognostic impact of pathway somatic mutation patterns in CLL. Materials and Methods: We focused on a cohort of 316 CLL patients defined by mutated IGHV with somatic mutation data gathered by International Cancer Genome Consortium. In this cohort we collected 4739 genes affected by nonsynonymous point and/or frameshift mutations. We performed gene set enrichment analysis to identify affected biological pathways, applied set theory to reduce redundancy in enriched gene sets, calculated pathway mutation scores for each patient and performed consensus clustering. Finally, we evaluated the difference in time to therapy (TTT) between identified CLL clusters. Results: We identified eight clusters differing in TTT (p&lt;0.0001); seven of these were characterized by distinct affected biological processes: namely, cell adhesion (21/23 mutated cases in the cluster), membrane depolarization (27/32), synapse organization (18/22), glycosylation (19/25), Rho protein signal transduction (27/37), oxytocin signalling and/or renin secretion (26/40), and transport through ABC transporters (11/20; patients with the earliest need for therapy). Conclusion: Among CLL patients with mutated IGHV we identified distinct subgroups with non-recurrently mutated genes involved in a limited number of biological pathways. Our findings have far-reaching implications for CLL diagnostics.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NV16-29447A" target="_blank" >NV16-29447A: Searching for mutations predisposing to familial hematologic and oncologic diseases</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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