Linked Life Data

17258789

Source:http://linkedlifedata.com/resource/pubmed/id/17258789

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-19
pubmed:abstractText
We evaluated alterations in p53, PIK3CA, PTEN, CTNNB1 (beta-catenin), MLH1, and BRAF among common histological subsets of epithelial ovarian tumors to characterize patterns of alterations of different molecular pathways. There were 12 clear cell, 26 endometrioid, and 51 serous carcinomas evaluated by direct DNA sequencing for mutations in p53, PIK3CA, PTEN, BRAF, and CTNNB1. Methylation-specific polymerase chain reaction (PCR) assessed MLH1 promoter methylation status. Quantitative PCR identified PIK3CA amplification in 22 EC/CC and 94 SC. p53 mutations were identified in 25 (49%) of 51 SC, 11 (42%) of 26 EC, and 1 (8.3%) of 12 CC neoplasms and were more common in grade 3 EC (P = .045) and advanced-stage EC/CC (P = .007). PIK3CA mutations were identified in 3 (25%) of 12 CC, 3 (12%) of 26 EC, and 0 of 51 SC. PTEN mutations were significantly more common in EC (8/26, 31%) compared with CC (0/12; P = .04) and SC (2/51, 4%; P = .002). CTNNB1 mutations were identified, 6 (23%) EC and no CC or SC (P = .008). Both PTEN and CTNNB1 mutations were more common in low-grade EC/CC, whereas PIK3CA mutations occurred only in grade 3 cancers. PTEN and PIK3CA mutations were more common in p53 wild-type tumors (P = .003). PIK3CA amplification occurred in fewer EC/CC (0/22) versus SC (19/94, 20%; P = 0.02) and were slightly more common in p53 wild-type compared with p53 mutant SC (P = .08). Of 26 EC, 22 (85%) had a mutation in one of the genes studied compared with 4 33% of 12 CC (P = .003). Women with EC/CC had significantly better overall survival (P = .0008), and this remained significant after accounting for stage (P=.04). Mutations in p53 or in PTEN/PIK3CA are alternative pathways in ovarian carcinogenesis. Activation of PIK3CA occurs by gene amplification in SC but via somatic mutation of PIK3CA or PTEN in EC and CC. PIK3CA mutations are associated with high-grade tumors, whereas PTEN and CTNNB1 mutations are associated with low-grade tumors. Mutations in p53, PIK3CA, PTEN, and CTNNB1 account for most EC tumors; most CC remain unexplained. EC/CC histology is a favorable prognostic factor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/BRAF protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/MLH1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PIK3CA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase, http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins B-raf, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0046-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-13
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Alternate molecular genetic pathways in ovarian carcinomas of common histological types.
pubmed:affiliation
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural