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Genetic characterisation of patients with multiple colonic polyps
  1. C Albuquerque1,
  2. M Cravo1,2,
  3. C Cruz3,
  4. P Lage2,
  5. P Chaves3,
  6. P Fidalgo2,
  7. A Suspiro2,
  8. C Nobre Leitão2
  1. 1Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia Francisco Gentil, 1093 Lisboa Codex, Portugal
  2. 2Serviço de Gastrenterologia, Instituto Português de Oncologia Francisco Gentil, 1093 Lisboa Codex, Portugal
  3. 3Departamento de Patologia Morfológica, Instituto Português de Oncologia Francisco Gentil, 1093 Lisboa Codex, Portugal
  1. Correspondence to:
 Dr C Albuquerque, Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia Francisco Gentil, Rua Prof Lima Basto, 1093 Lisboa Codex, Portugal;

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Two main hereditary colorectal cancer syndromes have been described, namely familial adenomatous polyposis coli (FAP) and hereditary non-polyposis colorectal cancer (HNPCC). FAP is a disease characterised by autosomal dominant inheritance where the affected subjects develop hundreds to thousands of adenomatous polyps throughout the whole colon, usually during their teenage years. This syndrome is also characterised by the development of a variable range of extracolonic manifestations.1,2 Germline mutations in the APC gene are responsible for FAP. Almost all mutations are nonsense or frameshift and result in the premature truncation of the protein.3–5 Patients with 5` or 3` mutations in the APC gene tend to present with fewer adenomas (0-100) and are described as having attenuated FAP (AAPC).6,7 HNPCC is also characterised by dominant inheritance and by the development of colorectal as well as various extracolonic cancers. Some studies have now shown that colorectal cancers (CRCs) in HNPCC patients also derive from precursor lesions, although the progression from adenoma to carcinoma is probably a much faster process compared to the sporadic and FAP model.8,9 HNPCC is caused by germline mutations in mismatch repair (MMR) genes, MSH2, MLH1, PMS1, PMS2, and MSH6. Accordingly, tumours originated through inactivation of the MMR pathway accumulate somatic mutations throughout the genome and especially in simple repeated sequences called microsatellites. Microsatellite instability (MSI) is the hallmark of most colorectal cancers (CRC) associated with HNPCC.

As previously reported,10–12 there are a substantial number of patients presenting with an excess of colorectal tumours, both adenomas and carcinomas, although they do not fulfil the diagnostic criteria for either FAP or HNPCC. These subjects usually present with fewer than 100 polyps, sometimes associated with synchronous or metachronic carcinomas, without accompanying extracolonic features and often with a poorly …

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