Linked Life Data

18715619

Source:http://linkedlifedata.com/resource/pubmed/id/18715619

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-11-17
pubmed:abstractText
Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of gastrointestinal tract often driven by oncogenic KIT exon 11 mutations. Although deletions and substitutions are most frequent KIT exon 11 mutations, duplications and insertions have been reported as well. In contrast to duplications, which cluster in 3'KIT exon 11, insertions affect 5'KIT, particularly codon 558. Clinicopathologic profile of gastrointestinal stromal tumors with insertions in codon 558 is not known. In this study, 17 gastrointestinal stromal tumors with codon 558 insertions are reported. Fifteen (88.2%) KIT codon 558 insertions consisted of 1694_1695insTCC leading to Lys558delinsAsnPro. However, 2 variant mutants Lys558delinsAsnGln and Lys558delinsAsnAsn were also identified. Based on analysis of inserted and flanking sequences, the insertions contain inverted DNA sequences of the opposite strand. Therefore, these insertions may develop due to a DNA strand switch during replication by DNA polymerases and by the effects of several different DNA repair processes. Patient median age was 61 years, and male-to-female ratio was 1:1.8. gastrointestinal stromal tumors were diagnosed in stomach (n = 4), small intestine (n = 7), and rectum (n = 3). Three tumors were disseminated and primary location could not be established. Fourteen tumors had spindle cell morphology, and epithelioid cell features were seen in 2 intestinal and 1 disseminated gastrointestinal stromal tumor. Based on size and mitotic activity, 2 (50%) of 4 gastric and 3 (48.9%) of 7 small intestinal gastrointestinal stromal tumors had more than 50% risk of metastases according to previous studies of gastrointestinal stromal tumor prognosis. All 3 rectal gastrointestinal stromal tumors were malignant. Metastases were verified in 8 (66.7%) of 12 patients with known clinical and follow-up data. In summary, KIT codon 558 insertions are rare mutations accounting for less than 1% of all KIT mutants. Gastrointestinal stromal tumors with these mutations appear to have predilection to female patients and intestinal location. Moreover, KIT codon 558 insertions might indicate an increased risk of malignant behavior for gastric gastrointestinal stromal tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1532-8392
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1728-36
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
KIT codon 558 insertions in gastrointestinal stromal tumors. Analysis of 17 rare KIT mutants.
pubmed:affiliation
Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA. lasota@afip.osd.mil
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Multicenter Study