Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00476876" target="_blank" >RIV/68378041:_____/17:00476876 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/bjc.2017.240" target="_blank" >http://dx.doi.org/10.1038/bjc.2017.240</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/bjc.2017.240" target="_blank" >10.1038/bjc.2017.240</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

Popis výsledku v původním jazyce

Background: A substantial fraction of familial colorectal cancer (CRC) and polyposis heritability remains unexplained. This study aimed to identify predisposing loci in patients with these disorders. nnMethods: Homozygosity mapping was performed using 222 563 SNPs in 302 index patients with various colorectal neoplasms and 3367 controls. Linkage analysis, exome and whole-genome sequencing were performed in a family affected by microsatellite stable CRCs. Candidate variants were genotyped in 10 554 cases and 21 480 controls. Gene expression was assessed at the mRNA and protein level. nnResults: Homozygosity mapping revealed a disease-associated region at 1q32.3 which was part of the linkage region 1q32.2-42.2 identified in the CRC family. This includes a region previously associated with risk of CRC. Sequencing identified the p.Asp1432Glu variant in the MIA3 gene ( known as TANGO1 or TANGO) and 472 additional rare, shared variants within the linkage region. In both cases and controls the population frequency was 0.02% for this MIA3 variant. The MIA3 mutant allele showed predominant mRNA expression in normal, cancer and precancerous tissues. Furthermore, immunohistochemistry revealed increased expression of MIA3 in adenomatous tissues. nnConclusions: Taken together, our two independent strategies associate genetic variations in chromosome 1q loci and predisposition to familial CRC and polyps, which warrants further investigation.

Název v anglickém jazyce

Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

Popis výsledku anglicky

Background: A substantial fraction of familial colorectal cancer (CRC) and polyposis heritability remains unexplained. This study aimed to identify predisposing loci in patients with these disorders. nnMethods: Homozygosity mapping was performed using 222 563 SNPs in 302 index patients with various colorectal neoplasms and 3367 controls. Linkage analysis, exome and whole-genome sequencing were performed in a family affected by microsatellite stable CRCs. Candidate variants were genotyped in 10 554 cases and 21 480 controls. Gene expression was assessed at the mRNA and protein level. nnResults: Homozygosity mapping revealed a disease-associated region at 1q32.3 which was part of the linkage region 1q32.2-42.2 identified in the CRC family. This includes a region previously associated with risk of CRC. Sequencing identified the p.Asp1432Glu variant in the MIA3 gene ( known as TANGO1 or TANGO) and 472 additional rare, shared variants within the linkage region. In both cases and controls the population frequency was 0.02% for this MIA3 variant. The MIA3 mutant allele showed predominant mRNA expression in normal, cancer and precancerous tissues. Furthermore, immunohistochemistry revealed increased expression of MIA3 in adenomatous tissues. nnConclusions: Taken together, our two independent strategies associate genetic variations in chromosome 1q loci and predisposition to familial CRC and polyps, which warrants further investigation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LD14050" target="_blank" >LD14050: Genetické a funkční determinanty nádorů tlustého střeva a konečníku a východiska k individualizované terapii</a><br>

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

British Journal of Cancer

ISSN

0007-0920

e-ISSN

—

Svazek periodika

117

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

1215-1223

Kód UT WoS článku

000412648600015

EID výsledku v databázi Scopus

2-s2.0-85028836164