RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373396" target="_blank" >RIV/00216208:11130/17:10373396 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/17:10373396

Result on the web

<a href="https://doi.org/10.1038/s41467-017-02177-w" target="_blank" >https://doi.org/10.1038/s41467-017-02177-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-02177-w" target="_blank" >10.1038/s41467-017-02177-w</a>

Result language

angličtina

Original language name

RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia

Original language description

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.

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

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OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Nature Communications [online]

ISSN

2041-1723

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

December

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

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UT code for WoS article

000418335100001

EID of the result in the Scopus database

2-s2.0-85038610246