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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Acknowledgments
This work was supported by the Norwegian Cancer Society. Highly appreciated is the contribution of late Professor Tobias Gedde-Dahl Jr who initiated the Norwegian Polyposis Project and the establishment of a national register at the Norwegian Cancer Register dedicated to Norwegian FAP families (www.kreftregisteret.no/en/The-Registries/Clinical-registries).
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This paper is dedicated to late Professor Tobias Gedde-Dahl (deceased in March 2006).
An erratum to this article can be found at http://dx.doi.org/10.1007/s00432-009-0631-3
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Andresen, P.A., Heimdal, K., Aaberg, K. et al. APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations. J Cancer Res Clin Oncol 135, 1463–1470 (2009). https://doi.org/10.1007/s00432-009-0594-4
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DOI: https://doi.org/10.1007/s00432-009-0594-4