Dataset Information

Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X.

ABSTRACT: Familial colorectal cancer type X (FCCTX) is characterized by clinical features of hereditary non-polyposis colorectal cancer with a yet undefined genetic background. Here we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX, using an integrative genomics strategy. Compared with wild-type protein, SEMA4A(V78M) demonstrates significantly increased MAPK/Erk and PI3K/Akt signalling as well as cell cycle progression of SEMA4A-deficient HCT-116 colorectal cancer cells. In a cohort of 53 patients with FCCTX, we depict two further SEMA4A mutations, p.Gly484Ala and p.Ser326Phe and the single-nucleotide polymorphism (SNP) p.Pro682Ser. This SNP is highly associated with the FCCTX phenotype exhibiting increased risk for colorectal cancer (OR 6.79, 95% CI 2.63 to 17.52). Our study shows previously unidentified germline variants in SEMA4A predisposing to FCCTX, which has implications for surveillance strategies of patients and their families.

SUBMITTER: Schulz E

PROVIDER: S-EPMC4214414 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X.

Schulz Eduard E Klampfl Petra P Holzapfel Stefanie S Janecke Andreas R AR Ulz Peter P Renner Wilfried W Kashofer Karl K Nojima Satoshi S Leitner Anita A Zebisch Armin A Wölfler Albert A Hofer Sybille S Gerger Armin A Lax Sigurd S Beham-Schmid Christine C Steinke Verena V Heitzer Ellen E Geigl Jochen B JB Windpassinger Christian C Hoefler Gerald G Speicher Michael R MR Boland C Richard CR Kumanogoh Atsushi A Sill Heinz H

Nature communications 20141013

Familial colorectal cancer type X (FCCTX) is characterized by clinical features of hereditary non-polyposis colorectal cancer with a yet undefined genetic background. Here we identify the SEMA4A p.Val78Met germline mutation in an Austrian kindred with FCCTX, using an integrative genomics strategy. Compared with wild-type protein, SEMA4A(V78M) demonstrates significantly increased MAPK/Erk and PI3K/Akt signalling as well as cell cycle progression of SEMA4A-deficient HCT-116 colorectal cancer cells ...[more]

PMID: 25307848

Dataset Information

Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X.

Publications

Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Similar Datasets

Germline Variants of CYBA and TRPM4 Predispose to Familial Colorectal Cancer.
| S-EPMC8833488 | biostudies-literature

Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X
| EGAS00001000957 | EGA

Germline EPHB2 receptor variants in familial colorectal cancer.
| S-EPMC2483346 | biostudies-literature

Whole exome sequencing identifies novel germline variants of SLC15A4 gene as potentially cancer predisposing in familial colorectal cancer.
| S-EPMC9250485 | biostudies-literature

New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients.
| S-EPMC7541943 | biostudies-literature

Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer.
| S-EPMC1181967 | biostudies-literature

Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.
| S-EPMC8381233 | biostudies-literature

Correspondence: SEMA4A variation and risk of colorectal cancer.
| S-EPMC4792923 | biostudies-literature

POT1 loss-of-function variants predispose to familial melanoma.
| S-EPMC4266105 | biostudies-literature

Familial Colorectal Cancer Type X.
| S-EPMC5635618 | biostudies-literature