Linked Life Data

17503413

Source:http://linkedlifedata.com/resource/pubmed/id/17503413

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-7-12
pubmed:abstractText
Hyperplastic Polyposis (HPPS) is a poorly characterized syndrome that increases colorectal cancer (CRC) risk. We aimed to provide a molecular classification of HPPS. We obtained 282 tumours from 32 putative HPPS patients with >or= 10 hyperplastic polyps (HPs); some patients also had adenomas and CRCs. We found no good evidence of microsatellite instability (MSI) in our samples. The epithelium of HPs was monoclonal. Somatic BRAF mutations occurred in two-thirds of our patients' HPs, and KRAS2 mutations in 10%; both mutations were more common in younger cases. The respective mutation frequencies in a set of 'sporadic' HPs were 18% and 10%. Importantly, the putative HPPS patients generally fell into two readily defined groups, one set whose polyps had BRAF mutations, and another set whose polyps had KRAS2 mutations. The most plausible explanation for this observation is that there exist different forms of inherited predisposition to HPPS, and that these determine whether polyps follow a BRAF or KRAS2 pathway. Most adenomas and CRCs from our putative HPPS patients had 'classical' morphology and few of these lesions had BRAF or KRAS2 mutations. These findings suggest that tumourigenesis in HPPS does not necessarily follow the 'serrated' pathway. Although current definitions of HPPS are sub-optimal, we suggest that diagnosis could benefit from molecular analysis. Specifically, testing BRAF and KRAS2 mutations, and perhaps MSI, in multiple polyps could help to distinguish HPPS from sporadic HPs. We propose a specific model which would have diagnosed five more of our cases as HPPS compared with the WHO clinical criteria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3417
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17503413-Adolescent, pubmed-meshheading:17503413-Adult, pubmed-meshheading:17503413-Aged, pubmed-meshheading:17503413-Cell Transformation, Neoplastic, pubmed-meshheading:17503413-Child, pubmed-meshheading:17503413-Colorectal Neoplasms, pubmed-meshheading:17503413-Female, pubmed-meshheading:17503413-Genetic Predisposition to Disease, pubmed-meshheading:17503413-Humans, pubmed-meshheading:17503413-Hyperplasia, pubmed-meshheading:17503413-Intestinal Mucosa, pubmed-meshheading:17503413-Intestinal Polyposis, pubmed-meshheading:17503413-Loss of Heterozygosity, pubmed-meshheading:17503413-Male, pubmed-meshheading:17503413-Middle Aged, pubmed-meshheading:17503413-Mutation, pubmed-meshheading:17503413-Neoplasm Proteins, pubmed-meshheading:17503413-Phenotype, pubmed-meshheading:17503413-Proto-Oncogene Proteins, pubmed-meshheading:17503413-Proto-Oncogene Proteins B-raf, pubmed-meshheading:17503413-ras Proteins
pubmed:year
2007
pubmed:articleTitle
Molecular classification and genetic pathways in hyperplastic polyposis syndrome.
pubmed:affiliation
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK. luis.carvajal@cancer.org.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Multicenter Study