Linked Life Data

17193822

Source:http://linkedlifedata.com/resource/pubmed/id/17193822

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-29
pubmed:abstractText
Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is becoming increasingly important, because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib mesylate) has become available. KIT mutations in GIST are clustered in four exons. Most common are exon 11 (juxtamembrane domain) mutations that include deletions, point mutations (affecting a few codons), and duplications (mostly in the 3' region). The latter mutations most often occur in gastric GISTs. Among gastric GISTs, tumors with deletions are more aggressive than those with point mutations; this does not seem to hold true in small intestinal GISTs. Exon 9 mutations (5-10%) usually are 2-codon 502-503 duplications, and these occur predominantly in intestinal versus gastric GISTs. Lesser imatinib sensitivity of these tumors has been noted. Kinase domain mutations are very rare; GISTs with such mutations are variably sensitive to imatinib. PDGFRA mutations usually occur in gastric GISTs, especially in the epithelioid variants; their overall frequency is approximately 30% to 40% of KIT mutation negative GISTs. Most common is exon 18 mutation leading Asp842Val at the protein level. This mutation causes imatinib resistance. Exon 12 and 14 mutations are rare. Most mutations are somatic (in tumor tissue only), but patients with familial GIST syndrome have consitutitonal KIT/PDGFRA mutations; >10 families have been reported worldwide with mutations generally similar to those in sporadic GISTs. GISTs in neurofibromatosis 1 patients, children, and Carney triad seem to lack GIST-specific KIT and PDGFRA mutations and may have a different disease mechanism. Secondary mutations usually occur in KIT kinase domains in patients after imatinib treatment resulting in resistance to this drug. Mutation genotyping is a tool in GIST diagnosis and in assessment of sensitivity to kinase inhibitors. This is a US government work. There are no restrictions on its use.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0740-2570
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-102
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17193822-Adolescent, pubmed-meshheading:17193822-Amino Acid Sequence, pubmed-meshheading:17193822-Antineoplastic Agents, pubmed-meshheading:17193822-Base Sequence, pubmed-meshheading:17193822-Child, pubmed-meshheading:17193822-Gastrointestinal Stromal Tumors, pubmed-meshheading:17193822-Humans, pubmed-meshheading:17193822-Molecular Conformation, pubmed-meshheading:17193822-Molecular Sequence Data, pubmed-meshheading:17193822-Mutation, pubmed-meshheading:17193822-Neurofibromatosis 1, pubmed-meshheading:17193822-Piperazines, pubmed-meshheading:17193822-Prognosis, pubmed-meshheading:17193822-Protein Structure, Tertiary, pubmed-meshheading:17193822-Proto-Oncogene Proteins c-kit, pubmed-meshheading:17193822-Pyrimidines, pubmed-meshheading:17193822-Receptor, Platelet-Derived Growth Factor alpha
pubmed:year
2006
pubmed:articleTitle
KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs).
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, Review