Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F18%3A00078035" target="_blank" >RIV/00209805:_____/18:00078035 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/18:00124644

Výsledek na webu

<a href="http://www.nature.com/articles/s41467-018-06541-2.pdf" target="_blank" >http://www.nature.com/articles/s41467-018-06541-2.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-018-06541-2" target="_blank" >10.1038/s41467-018-06541-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia

Popis výsledku v původním jazyce

Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P=1.36 x 10(-)(54)) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 x 10(-)(19)) . Both risk alleles are observed at a low frequency among controls (similar to 2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

Název v anglickém jazyce

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenstrom macroglobulinemia

Popis výsledku anglicky

Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P=1.36 x 10(-)(54)) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 x 10(-)(19)) . Both risk alleles are observed at a low frequency among controls (similar to 2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/LO1413" target="_blank" >LO1413: RECAMO2020</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Nature communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

4182

Kód UT WoS článku

000446846600001

EID výsledku v databázi Scopus

2-s2.0-85054606609