Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schulz, E; Klampfl, P; Holzapfel, S; Janecke, AR; Ulz, P; Renner, W; Kashofer, K; Nojima, S; Leitner, A; Zebisch, A; Wölfler, A; Hofer, S; Gerger, A; Lax, S; Beham-Schmid, C; Steinke, V; Heitzer, E; Geigl, JB; Windpassinger, C; Hoefler, G; Speicher, MR; Boland, CR; Kumanogoh, A; Sill, H.
Germline variants in the SEMA4A gene predispose to familial colorectal cancer type X.
Nat Commun. 2014; 5(10):5191-5191
Doi: 10.1038/ncomms6191
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- Führende Autor*innen der Med Uni Graz
- Schulz Eduard
- Sill Heinz
- Co-Autor*innen der Med Uni Graz
- Beham-Schmid Christine
- Geigl Jochen Bernd
- Gerger Armin
- Heitzer Ellen
- Höfler Gerald
- Kashofer Karl
- Leitner Anita
- Renner Wilfried
- Speicher Michael
- Ulz Peter
- Windpassinger Christian
- Wölfler Albert
- Zebisch Armin
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Amino Acid Sequence -
- Colorectal Neoplasms - genetics
- Female -
- Genetic Predisposition to Disease -
- Genetic Variation -
- Germ Cells - metabolism
- Humans -
- Male -
- Middle Aged -
- Molecular Sequence Data -
- Mutation, Missense -
- Phorbols -
- Semaphorins - chemistry
- Sequence Alignment -