Reference Detail

Request Content

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Ref Type Journal Article
PMID (23456621)
Authors Gao J, Tian Y, Li J, Sun N, Yuan J, Shen L
Title Secondary mutations of c-KIT contribute to acquired resistance to imatinib and decrease efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors.
Journal Vol Issue Date Pages Journal Short Title
Medical oncology (Northwood, London, England) 30 2 2013 Jun 522 Med Oncol
URL
Abstract Text The aim of this study was to investigate the associations between secondary mutations of c-KIT/PDGFRα and acquired imatinib resistance or efficacy of sunitinib in Chinese patients with gastrointestinal stromal tumors (GISTs). Mutations of c-KIT (exons 9, 11, 13, 14, 17, and 18) and PDGFRα (exons 12 and 18) in tumor samples of 50 patients were analyzed by direct sequencing. A total of 50 samples before imatinib and 52 samples after imatinib were collected. Among 52 samples after imatinib, 38 samples were imatinib resistant and 14 samples were imatinib sensitive. All patients before imatinib treatment had primary mutations of c-KIT exon 11 (n = 45) or exon 9 (n = 5), and no PDGFRα mutations were found in these patients. After imatinib treatment, 25 of 38 (65.8 %) resistant tumors had secondary mutations in c-KIT exon 13 (n = 10), exon 14 (n = 1), exon 17 (n = 12) and exon 18 (n = 2), while no secondary mutations of c-KIT were found in 14 sensitive tumors (P < 0.001), indicating the close association of c-KIT secondary mutations with imatinib-acquired resistance. In our study, 19 patients received sunitinib treatment after the failure of imatinib, and it seemed that the median progression-free survival (7 vs. 19 months, P = 0.244) in patients with secondary mutations (n = 13) was lower than that in patients without secondary mutations (n = 6). Secondary mutations of c-KIT were significantly associated with acquired resistance to imatinib in Chinese GIST patients, and whether secondary mutations of c-KIT could influence the efficacy of sunitinib needed to be further investigated.

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT exon11 KIT exon17 gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, 65.8% (25/38) of patients with a gastrointestinal stromal tumor harboring a primary KIT mutation in exon 11 or exon 9 progressed on treatment with Gleevec (imatinib) and 12 of the 25 patients were found to have acquired a secondary KIT mutation in exon 17 (PMID: 23456621). 23456621
KIT exon11 KIT V654A gastrointestinal stromal tumor predicted - resistant Imatinib Case Reports/Case Series Actionable In a clinical study, 65.8% (25/38) of patients with a gastrointestinal stromal tumor harboring a primary KIT mutation in exon 11 or exon 9 progressed on treatment with Gleevec (imatinib) and 10 of the 25 patients were found to have acquired a secondary mutation in exon 13, KIT V654A (PMID: 23456621). 23456621