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Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.10.2009 | Original Paper

APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations

verfasst von: Per Arne Andresen, Ketil Heimdal, Kristin Aaberg, Kristin Eklo, Sarah Ariansen, Alexandra Silye, Olav Fausa, Lars Aabakken, Stefan Aretz, Tor J. Eide, Tobias Gedde-Dahl Jr.

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2009

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Abstract

Introduction

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease caused by mutations in the adenomatous polyposis coli (APC) gene. Massive formation of colorectal adenomas, of which some will inevitably develop into adenocarcinomas, is the hallmark of the disease. Characterization of causative APC mutations allows presymptomatic diagnosis, close follow-up and prophylactic intervention in families. To date more than 900 different germline mutations have been characterized worldwide demonstrating allelic heterogeneity.

Purpose

The germline mutation spectrum of APC identified in 69 apparently unrelated Norwegian FAP families are presented and discussed with reference to clinical phenotype and novel mutation rate.

Methods

Different methods have been used over the years. However, all mutations were confirmed detectable by an implemented denaturing high-performance liquid chromatography screening approach. Multiplex ligation-dependent probe amplification analysis was employed for potential gross rearrangements.

Results

Fifty-three distinctive mutations were detected, of which 22 have been detected in Norway exclusively. Except for two major deletion mutations encompassing the entire APC, all mutations resulted in premature truncation of translation caused by non-sense (31%) or change in reading frame (69%).

Conclusion

A high ratio of novel APC mutations continues to contribute to APC mutation heterogeneity causing FAP. This is the first comprehensive report of APC germline mutation spectrum in Norway.

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Titel: APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations
verfasst von: Per Arne Andresen
Ketil Heimdal
Kristin Aaberg
Kristin Eklo
Sarah Ariansen
Alexandra Silye
Olav Fausa
Lars Aabakken
Stefan Aretz
Tor J. Eide
Tobias Gedde-Dahl Jr.
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0594-4

Springer Medizin

APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations