ArticleGut2006
Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation.
Article in Gut, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 104 citations in OpenAlex.
- Review
- Familial Adenomatous Polyposis-Risk of Cancer, Cancer Prevention, and Long-Term Consequences: Learnings from Five Decades with the Danish Polyposis Register.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026Review
- The c.1744G > C, p.(Glu582Gln) missense variant in coding exon 14 of APC increases skipping of a natural occurring isoform and causes Familial Adenomatous Polyposis.Journal of cancer research and clinical oncology · 2025Article
- Early genetic events in the colorectal carcinogenic pathway of familial adenomatous polyposis and sporadic polyp: germline and somatic alterations in carcinogenesis.Frontiers in genetics · 2025Article
- Endoscopic indicators in patients with familial adenomatous polyposis undergoing duodenal resections - a nationwide Danish cohort study with long-term follow-up.Familial cancer · 2024Article
- Gastrointestinal Cancer Precursor Conditions and Their Detection.Hematology/oncology clinics of North America · 2024Review
- Usefulness of genotyping APC gene for individualizing management of patients with familial adenomatous polyposis.International journal of clinical oncology · 2023Article
- De novo myelodysplastic syndrome in a Rothmund-Thomson Syndrome patient with novel pathogenicBlood science (Baltimore, Md.) · 2023Article
- Morphological Analyses of Colorectal Adenocarcinomas in Japanese Familial Adenomatous Polyposis Patients.Journal of the anus, rectum and colon · 2022Article
- CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC.Hereditary cancer in clinical practice · 2021Article
- Novel Pathogenic Germline Variant of the Adenomatous Polyposis Coli (APC) Gene, p.S2627Gfs*12 Identified in a Mild Phenotype of APC-Associated Polyposis: A Case Report.The American journal of case reports · 2020Article
- Autocatalytic Tissue Polymerization Reaction Mechanism in Colorectal Cancer Development and Growth.Cancers · 2020Article
- A rare missense variant inHereditary cancer in clinical practice · 2020Article
- Current status of the genetic susceptibility in attenuated adenomatous polyposis.World journal of gastrointestinal oncology · 2019Review
- Attenuated familial adenomatous polyposis (AFAP) in a patient associated with a novel mutation in APC.BMJ case reports · 2019Article
- APC mosaicism in a young woman with desmoid type fibromatosis and familial adenomatous polyposis.Familial cancer · 2018Article
- Wnt Signaling and Colorectal Cancer.Current colorectal cancer reports · 2017Article
- β-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS).Journal of clinical pathology · 2016Article
- Copy number of the Adenomatous Polyposis Coli gene is not always neutral in sporadic colorectal cancers with loss of heterozygosity for the gene.BMC cancer · 2016Article
- Genomic era diagnosis and management of hereditary and sporadic colon cancer.World journal of clinical oncology · 2014Review
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Authors and funding
23 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundAttenuated familial adenomatous polyposis (AFAP) is associated with germline mutations in the 5', 3', and exon 9 of the adenomatous polyposis coli (APC) gene. These mutations probably encode a limited amount of functional APC protein. METHODS AND
resultsWe found that colonic polyp number varied greatly among AFAP patients but members of the same family tended to have more similar disease severity. 5' Mutants generally had more polyps than other patients. We analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from 35 patients (16 families) with a variety of AFAP associated germline mutations. In common with two previous studies of individual kindreds, we found biallelic changes ("third hits") in some polyps. We found that the "third hit" probably initiated tumorigenesis. Somatic mutation spectra were similar in 5' and 3' mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast, "third hits" were more common. Most "third hits" left three 20 amino acid repeats (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic mutation) of the wild-type allele; but some polyps had loss of the germline mutant with mutation leaving one 20AAR on the wild-type allele.
conclusionsWe propose that mutations, such as nt4661insA, that leave three 20AARs are preferentially selected in cis with some AFAP mutations because the residual protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to need "three hits" however. AFAP is phenotypically and genetically heterogeneous. In addition to effects of different germline mutations, modifier genes may be acting on the AFAP phenotype, perhaps influencing the quantity of functional protein produced by the germline mutant allele.
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