KIT

Overview

KIT is a receptor tyrosine kinase and a canonical oncogenic driver in GIST, mastocytosis, and germ cell tumors.

Alterations observed in the corpus

  • Oncogenic KIT mutations observed in a minority of female germ cell tumors profiled by MSK-IMPACT; mostly clonal by WES PMID:36862133.
  • KIT exon 11 mutation status was incorporated into the gastric GIST elastic-net Cox genomic risk model (n=152 primary localized gastric GISTs); absence of KIT exon 11 mutation flagged intermediate risk for recurrence PMID:37477937.
  • KIT amplification was detected exclusively in sporadic ANGS but absent in radiation-associated (RT) angiosarcoma (n=44 RT-AS, n=135 sporadic AS) in the MSK RT-sarcoma comparative genomic study PMID:37350195.
  • Recurrent activating KIT mutations observed in GIST samples and unexpectedly in one myxoid/round-cell liposarcoma (MRLS) in a 207-patient multi-subtype sarcoma sequencing study (sarc_mskcc); GIST/KIT biology cited as the imatinib precedent motivating subtype-specific sarcoma therapy PMID:20601955.
  • Somatic activating mutations in 56% of GISTs; one germline P/LP variant (p.Lys509Ile) identified in paired tumor-normal sequencing PMID:36593350
  • 21-bp in-frame deletion in exon 11 detected in acral melanoma ME032; KIT exon 11 mutations in acral melanoma may confer sensitivity to imatinib PMID:22622578
  • Somatic mutations detected in melanoma WES cohort (Broad, 121 tumors) PMID:22817889
  • Copy-number gain observed in lung squamous cell carcinoma (178 tumors, TCGA) PMID:22960745
  • Mutations including codon 761 (likely activating) and copy-number gain in SCLC (36 tumors, JHU WES/WGS) PMID:22941189
  • Copy-number amplification in Basal-like breast cancer; listed among druggable RTK targets (alongside FGFR1/2, IGF1R, MET, PDGFRA) in TCGA 510-tumor analysis PMID:23000897
  • Non-FLT3 activated signaling gene contributing to the 59% signaling-pathway prevalence in AML; part of the KIT/KRAS/NRAS/PTPN11 non-FLT3 signaling subgroup; already incorporated in current AML classification alongside FLT3, NPM1, and CEBPA PMID:23634996
  • KIT-high (by IHC) status showed a non-significant trend toward greater sorafenib benefit in the SHARP biomarker substudy in HCC (combined with low plasma HGF), but no predictive biomarker for sorafenib has been validated. PMID:24798001
  • KIT mutations occur in ~10% of thymic carcinomas (literature context); three GTF2I-mutant thymic carcinomas in the study cohort were all KIT-positive by IHC, including two squamous cell and one undifferentiated carcinoma. PMID:24952746
  • KIT mutations occur in ~10% of thymic carcinomas (literature); all three GTF2I-mutant thymic carcinomas in this NCI cohort were KIT-positive by IHC; cited as a potential targetable lesion but not directly evaluated for targeted therapy response in this study. PMID:24974848
  • KIT E562D (exon 11, canonical GIST hotspot region) was identified as an activating oncogene mutation in metastatic cutaneous squamous cell carcinoma (n=29 lymph-node metastases); activating events across 12 oncogenes were nearly mutually exclusive. PMID:25589618
  • KIT alteration in 1% of HCC (243-case European WES cohort); listed as FDA-targetable alteration in the HCC druggable landscape PMID:25822088
  • KIT mutations and 4q12 focal amplifications enriched in Triple-WT cutaneous melanoma (TCGA 333-sample cohort); highest KIT protein abundance in Triple-WT by RPPA; rationale for imatinib and dasatinib; co-amplified with PDGFRA and KDR at 4q12 PMID:26091043
  • Rare oncogenic kinase mutation (with BRAF and PIK3CA) found in SCLC (4 tumors total); considered a potential targeted-therapy candidate PMID:26168399
  • Identified as a marker of the reactive-like ILC mRNA subtype (with high EGFR expression) in a comprehensive molecular analysis of invasive lobular carcinoma PMID:26451490
  • KIT serves as a luminal epithelial cell marker by immunohistochemistry in adenoid cystic carcinoma (ACC); used to identify luminal vs. myoepithelial cell compartments in low-grade ACC (n=20 WGS tumors) PMID:26829750
  • Amplification at PDGFRA/KIT/KDR locus is among the candidate Ras/Raf/RTK pathway events that raise the fraction of lung ADCs with an actionable driver to 76%; enriched in oncogene-negative lung ADC PMID:27158780
  • KIT is a member of the chromatin-spliceosome AML subgroup context; the AML cohort of 1540 patients identified KIT among the 76 driver genes/regions with 5234 total driver mutations PMID:27276561
  • KIT co-amplified with PDGFRA and KDR in 4 ACYC patients treated with regorafenib, in a cohort of 151 advanced head and neck tumors profiled by MSK-IMPACT 410-gene panel PMID:27442865
  • KIT hotspot mutations in 19/180 patients (10.6%), mostly exon 17; enriched in seminoma (SEM) versus nonseminoma (29.6% vs 4%; P<.001); imatinib-resistance pattern distinct from GIST; targeted by imatinib/sunitinib as candidate therapy in cisplatin-resistant germ cell tumors PMID:27646943
  • KIT Asn655Lys activating mutation in a 7-year-old with AML yielded near-complete peripheral blood blast clearance with palliative imatinib sustained over 9 months; a second AML patient harbored KIT D816H (c.2446G>C) co-occurring with TET2 and FLT3 variants PMID:28007021.
  • 1 patient with exon 9 E490Q mutation (previously described in thymic carcinoma) in prospective LUAD cohort (860 patients, MSK-IMPACT) PMID:28336552
  • Single L576P mutation in 1 patient in acral lentiginous melanoma (ALM) integrated genomic study (34 patients) PMID:28373299

Cancer types (linked)

  • OGCT — oncogenic KIT mutations in a subset of female GCT cases in the Make-an-IMPACT rare-cancer cohort PMID:36862133.
  • ANGS — KIT amplification exclusive to sporadic AS, absent in RT-AS PMID:37350195.

Co-occurrence and mutual exclusivity

  • None reported.

Therapeutic relevance

  • Not directly targeted in the reported female GCT cases PMID:36862133.

Open questions

  • Whether KIT-mutant female GCTs derive benefit from KIT inhibitors is not addressed PMID:36862133.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36593350

This page was processed by crosslinker on 2026-05-14. - PMID:22622578

This page was processed by crosslinker on 2026-05-14. - PMID:22817889

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:22941189

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:23634996

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:24952746

This page was processed by crosslinker on 2026-05-14. - PMID:24974848

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26168399

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14. - PMID:26829750

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27276561

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14. - PMID:28373299

This page was processed by wiki-cli on 2026-05-14.