Gene:
KIT
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for imatinib and ABL1, BCR, KIT

This label is on the FDA Biomarker List
Genetic testing required

Summary

The decision of whether to treat patients with imatinib is based on the presence of genetic biomarkers, including BCR-ABL (the Philadelphia chromosome), KIT, and PDGFR gene rearrangements.

Annotation

The decision of whether to treat patients with imatinib is based on the presence of genetic biomarkers, including BCR-ABL (the Philadelphia chromosome), KIT, and PDGFR gene rearrangements.

Excerpt from the imatinib drug label:

Gleevec is a kinase inhibitor indicated for the treatment of:
Newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
. . .
Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5)
Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6)
. . .
Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (1.9)
Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10)

If patients must be administered a strong CYP3A4 inducer, based on pharmacokinetic studies, the dosage of Gleevec should be increased by at least 50%, and clinical response should be carefully monitored.

Imatinib is an inhibitor of the BCR-ABL tyrosine kinase that is created by the Philadelphia chromosome rearrangement in chronic myeloid leukemia. Imatinib also inhibits the kinases encoded by the PDGFRB and KIT genes. The KIT:D816V mutation, found in many patients with aggressive systemic mastocytosis, is a gain-of-function mutation that is resistant to treatment with imatinib.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the imatinib drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Gastrointestinal Stromal Tumors
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Glioma
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Heart Failure
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Leukemia
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Leukemia, Myeloid
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Leukemia, Myeloid, Acute
    • Indications & usage section, Warnings section
    • source: PHONT
  • Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Philadelphia Chromosome
    • Indications & usage section, Dosage & administration section, dosage, efficacy
    • source: FDA Label
  • CYP2D6
    • Drug interactions section, Clinical pharmacology section, metabolism/PK
    • source: FDA Label
  • CYP3A4
    • Dosage & administration section, Drug interactions section, Clinical pharmacology section, dosage, metabolism/PK
    • source: FDA Label
  • KIT
    • Indications & usage section, Dosage & administration section, Clinical pharmacology section, Clinical studies section, dosage, efficacy
    • source: FDA Label

last updated 10/25/2013

European Medicines Agency (EMA) Label for imatinib and ABL1, BCR, FIP1L1, KIT, PDGFRB

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for imatinib (Glivec) contains pharmacogenetic information regarding the indication of the drug in patients with tumors positive for biomarkers including KIT (CD117), BCR-ABL (Philadelphia chromosome), PDGFR and FIP1L1-PDGFRalpha rearrangements.

Annotation

Excerpt from the imatinib (Glivec) EPAR:

Glivec is indicated for the treatment of

  • adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment.
  • adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis.
  • adult patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy.
  • adult patients with relapsed or refractory Ph+ ALL as monotherapy.
  • adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
  • adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFR rearrangement.

Glivec is indicated for

  • the treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST).
  • the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment.

This information is highlighted in the following sections:
Therapeutic indications, posology and method of administration, pharmacodynamic properties, package leaflet: information for the user.

The label also states that caution be taken when imatinib is taken concomittantly with CYP3A4 inhibitors and CYP3A4 inducers should be avoided.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the imatinib EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

Overview

Alternate Names:  None
Alternate Symbols:  C-Kit; CD117; SCFR
PharmGKB Accession Id: PA30128

Details

Cytogenetic Location: chr4 : q11 - q12
GP mRNA Boundary: chr4 : 55524095 - 55606881
GP Gene Boundary: chr4 : 55514095 - 55609881
Strand: plus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Curated Information ?

Evidence Gene
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
HRAS
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
KRAS
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
NRAS

Curated Information ?

Evidence Drug
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
imatinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
sorafenib
No related diseases are available

Publications related to KIT: 14

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rho Kinase Regulates the Survival and Transformation of Cells Bearing Oncogenic Forms of KIT, FLT3, and BCR-ABL. Cancer cell. 2011. Mali Raghuveer Singh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proceedings of the National Academy of Sciences of the United States of America. 2009. Gajiwala Ketan S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Heinrich Michael C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Tumor suppressor FUS1 signaling pathway. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2008. Ji Lin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cancer and leukemia group B gastrointestinal cancer committee. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Goldberg Richard M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gain-of-Function Mutations of Receptor Tyrosine Kinases in Gastrointestinal Stromal Tumors. Current genomics. 2006. Isozaki K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. The Journal of biological chemistry. 2004. Mol Clifford D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Imatinib mesylate--a new oral targeted therapy. The New England journal of medicine. 2002. Savage David G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science (New York, N.Y.). 1998. Hirota S, et al. PubMed

LinkOuts

UniProtKB:
KIT_HUMAN (P10721)
Q6IQ28_HUMAN (Q6IQ28)
Ensembl:
ENSG00000157404
GenAtlas:
KIT
GeneCard:
KIT
MutDB:
KIT
ALFRED:
LO017051O
HuGE:
KIT
Comparative Toxicogenomics Database:
3815
ModBase:
P10721
HumanCyc Gene:
HS08211
HGNC:
6342

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