Print Email Facebook Twitter APC mutations in sporadic coloretal carcinomas from The Netherlands Cohort Study Title APC mutations in sporadic coloretal carcinomas from The Netherlands Cohort Study Author Lüchtenborg, M. Weijenberg, M.P. Roemen, G.M.J.M. de Bruïne, A.P. van den Brandt, P.A. Lentjes, M.H.F.M. Brink, M. van Engeland, M. Goldbohm, R.A. de Goeij, A.F.P.M. TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO Publication year 2004 Abstract The adenomatous polyposis coli (APC) gene is considered to be a gatekeeper in colorectal tumourigenesis. Inactivating mutations in APC have been reported in 34-70% of sporadic colorectal cancer patients, the majority of which occur in the mutation cluster region (MCR). In this study, tumour tissue from 665 incident colorectal cancer patients, who originate from 120 852 men and women (55-69 years of age at baseline) participating in The Netherlands Cohort Study, was evaluated for the occurrence and type of APC mutations with regard to age at diagnosis, gender, family history of colorectal cancer, Dukes' stage, tumour differentiation and sub-localization. Mutation analysis of the MCR, which spans codons 1286-1513, was performed on archival adenocarcinoma samples using macrodissection, nested PCR and direct sequencing of purified PCR fragments. A large number of genetic aberrations (n = 978), including point mutations (n = 833), deletions (n = 126) and insertions (n = 19) was detected in the MCR in 72% of patients (479/665). In particular, we observed a large number of missense mutations, more than reported previously. This may indicate involvement in colorectal carcinogenesis, although their significance for APC functions is unclear. Truncating mutations were found in 37% of patients (248/665). Patients with rectosigmoid and rectum tumours relatively more frequently harboured C > T nonsense mutations and truncating frameshift mutations as compared with patients with proximal and distal colon tumours (P = 0.009 and P = 0.045, respectively). Differences in occurrence of truncating mutations with regard to tumour sublocalization suggest a different aetiology of tumourigenesis in colon and rectum. © Oxford University Press 2004; all rights reserved. Subject HealthFood and Chemical Risk AnalysisAPC proteinAdultAgedAscending colonCancer localizationCancer stagingCarcinogenesisCodonCohort analysisColon adenocarcinomaColorectal carcinomaControlled studyDescending colonFamily historyFemaleFrameshift mutationGenderGene clusterGene deletionGene functionGene insertionGene mutationHumanHuman tissueMajor clinical studyMaleMicrodissectionMissense mutationMutational analysisNetherlandsNonsense mutationOnset agePoint mutationPolymerase chain reactionPriority journalRectum carcinomaReviewSequence analysisTumor differentiationTumor localizationAdenomatous Polyposis Coli ProteinAmino Acid SequenceBase SequenceCarcinomaColorectal NeoplasmsFrameshift MutationMiddle AgedSequence Deletion To reference this document use: http://resolver.tudelft.nl/uuid:25aee0de-cb30-42c8-8825-a82f8373d049 DOI https://doi.org/10.1093/carcin/bgh117 TNO identifier 237898 ISSN 0143-3334 Source Carcinogenesis, 25 (7), 1219-1226 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.