Gene Variant Detail

Gene KIT
Variant A502_Y503dup
Impact List duplication
Protein Effect gain of function
Gene Variant Descriptions KIT A502_Y503dup (also referred to as Y503_F504insAY) indicates the insertion of 2 duplicate amino acids, alanine (A)-502 through tyrosine (Y)-503, in the Ig-like C2-type domain 5 of the Kit protein (UniProt.org). A502_Y503dup results in constitutive phosphorylation of Kit and is transforming in cell culture (PMID: 15790786, PMID: 19865100).
Associated Drug Resistance

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Transcript NM_000222
gDNA chr4:g.54726014_54726019
cDNA c.1504_1509
Protein p.A502_Y503
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001093772 chr4:g.54726014_54726019 c.1504_1509 p.A502_Y503 RefSeq GRCh38/hg38
XM_017008178 chr4:g.54726014_54726019 c.1504_1509 p.A502_Y503 RefSeq GRCh38/hg38
NM_000222 chr4:g.54726014_54726019 c.1504_1509 p.A502_Y503 RefSeq GRCh38/hg38
XM_017008180 chr4:g.54726014_54726019 c.1504_1509 p.A502_Y503 RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (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 a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT A502_Y503dup PDGFRA H687Y gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, PDGFRA H687Y was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring primary KIT A502_Y503dup, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor predicted - resistant Sunitinib Preclinical - Pdx Actionable In a preclinical study, Sutent (sunitinib) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (26.2%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup KIT D820E gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, Gleevec (imatinib mesylate) did not inhibit Kit, Erk, or Mtor signaling and resulted in minimal (7.4%) tumor inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup gastrointestinal stromal tumor resistant Imatinib Preclinical - Pdx Actionable In a preclinical study, a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup demonstrated resistance to treatment with Gleevec (imatinib), resulting in increased tumor volume (PMID: 27777285). 27777285
KIT A502_Y503dup gastrointestinal stromal tumor sensitive Cabozantinib Preclinical - Pdx Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) resulted in decreased tumor volume and reduced mitotic activity in a gastrointestinal stromal tumor patient derived xenograft (PDX) model harboring KIT A502_Y503dup (PMID: 27777285). 27777285
KIT A502_Y503dup gastrointestinal stromal tumor predicted - sensitive Regorafenib Preclinical - Pdx Actionable In a preclinical study, Stivarga (regorafenib) did not significantly inhibit Kit, Erk, or Mtor signaling, but resulted in tumor growth inhibition in patient-derived xenograft (PDX) model of gastrointestinal stromal tumor harboring KIT A502_Y503dup and KIT D820E, which was established from a patient who did not respond to Gleevec (imatinib mesylate) and Sutent (sunitinib) (PMID: 29100343). 29100343
KIT A502_Y503dup Advanced Solid Tumor sensitive Flumatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Flumatinib in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Sutent (sunitinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup Advanced Solid Tumor sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT A502_Y503dup (Y503_F504insAY) were sensitive to Gleevec (imatinib) in culture, demonstrating decreased cell proliferation (PMID: 24205792). 24205792
KIT A502_Y503dup KIT N822K gastrointestinal stromal tumor predicted - resistant Imatinib Clinical Study Actionable In a clinical study, KIT N822K was identified as a secondary mutation in a patient with gastrointestinal stromal tumor harboring a primary KIT A502_Y503dup, who developed resistance to Gleevec (imatinib mesylate) (PMID: 18488160). 18488160