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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00064203:_____/17:10373396

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Nature Communications [online]

ISSN

2041-1723

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

—

Kód UT WoS článku

000418335100001

EID výsledku v databázi Scopus

2-s2.0-85038610246