Reference Detail

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@jax.org

Ref Type
PMID (33212994)
Authors Fornasarig M, Gasparotto D, Foltran L, Campigotto M, Lombardi S, Del Savio E, Buonadonna A, Puglisi F, Sulfaro S, Canzonieri V, Cannizzaro R, Maestro R
Title A Novel Kindred with Familial Gastrointestinal Stromal Tumors Caused by a Rare KIT Germline Mutation (N655K): Clinico-Pathological Presentation and TKI Sensitivity.
Journal Journal of personalized medicine
Vol 10
Issue 4
Date 2020 Nov 17
URL
Abstract Text Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are characterized by activating mutations in KIT or PDGFRA genes. The vast majority of GISTs are sporadic, but rare hereditary forms have been reported, often featuring multifocality and younger age of onset. We here report the identification of a novel kindred affected by familial GIST caused by a KIT germline mutation in exon 13 (N655K). No family affected by hereditary GIST due to this KIT variant has been reported in literature so far. We were able to track the mutation in three members of the family (proband, mother, and second-degree cousin), all affected by multiple GISTs. Due to its rarity, the N655K variant is poorly characterized. We conducted in vitro drug sensitivity assays that indicated that most tyrosine kinase inhibitors (TKIs) currently included in the therapeutic armamentarium for GISTs have a limited inhibitory activity toward this mutation. However, when compared to a classical imatinib-resistant KIT mutation (T670I), N655K was slightly more sensitive to imatinib, and encouraging responses were observed with last-generation TKIs.

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"

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 T670I Advanced Solid Tumor resistant Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T670I were resistant to treatment with Gleevec (imatinib) in culture (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor predicted - sensitive Imatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Gleevec (imatinib) treatment in culture, resulting in reduced cell viability at high treatment dosages (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor decreased response Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Cometriq (Cabometyx, cabozantinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor predicted - sensitive Avapritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Ayvakit (avapritinib) in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). 33212994
KIT T670I Advanced Solid Tumor sensitive Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Stivarga (regorafenib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). 33212994
KIT T670I Advanced Solid Tumor sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Sutent (sunitinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). 33212994
KIT N655K gastrointestinal stromal tumor predicted - sensitive Imatinib Case Reports/Case Series Actionable In a clinical case study, a patient with gastrointestinal stromal tumor (GIST) harboring a germline KIT N655K mutation, associated with hereditary GIST syndrome, demonstrated slow disease progression for 12 months while on treatment with Gleevec (imatinib) at 400mg/d, and upon disease progression following surgery and 15 months of Sutent (sunitinib) treatment, was rechallenged with Gleevec (imatinib) at 800mg/d and remained stable for a further 9 months (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor decreased response Sunitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Sutent (sunitinib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor decreased response Regorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated a reduced response to Stivarga (regorafenib) treatment compared to cells expressing KIT T670I in culture (PMID: 33212994). 33212994
KIT W557_K558del Advanced Solid Tumor sensitive Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, Cometriq (Cabometyx, cabozantinib) treatment resulted in decreased viability of transformed cells expressing KIT W557_K558del in culture (PMID: 33212994). 33212994
KIT N655K Advanced Solid Tumor predicted - sensitive Ripretinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT N655K demonstrated some sensitivity to Qinlock (ripretinib) treatment in culture, but were less sensitive than cells expressing KIT W557_K558del (PMID: 33212994). 33212994
KIT T670I Advanced Solid Tumor sensitive Cabozantinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing KIT T670I demonstrated sensitivity to Cometriq (Cabometyx, cabozantinib) treatment in culture, resulting in reduced cell viability (PMID: 33212994). 33212994