Linked Life Data

18294292

Source:http://linkedlifedata.com/resource/pubmed/id/18294292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-4-1
pubmed:abstractText
Although imatinib showed high activity for advanced gastrointestinal stromal tumor (GIST) and improved the prognosis of GIST patients, resistance to the drug appears with prolonged use. Mechanisms of acquired resistance are still under investigation. In the present study, we carried out histologic and genetic analysis of 45 secondary resistant lesions obtained from 25 Japanese GIST patients treated with imatinib. All resistant lesions showed viable tumor cells expressing KIT protein, whereas imatinib-sensitive lesions did not. All pre-imatinib samples have KIT mutations either in exon 9 (n = 3) or exon 11 (n = 22), identified in the KIT gene of corresponding resistant tumors. In addition to primary mutations, 33 out of 45 tumors (73%) showed secondary KIT mutations in the kinase domain of the KIT gene. Secondary mutations are missense mutations and are mostly located in the kinase domains of the same allele to the primary mutations (cis-position). Resistant lesions showed monoclonal development of tumor cells. Taken together, additional cis-positioned mutations in the kinase domains are a major cause of secondary resistance to imatinib in Japanese GIST patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1349-7006
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
799-804
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor.
pubmed:affiliation
Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan. toshin@surg1.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't