Gene:
RET
ret proto-oncogene

On ACMG incidental findings list

On ACMG incidental findings list

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 08/06/2014

European Medicines Agency (EMA) Label for vandetanib and RET

Genetic testing recommended

Summary

The EMA European Public Assessment Report (EPAR) for vandetanib (Caprelsa) recommends testing for RET mutation status, as patients without RET mutations may have decreased benefit from vandetanib treatment.

Annotation

Vandetanib is indicated in patients with unresectable locally advanced or metastatic medullary thyroid cancer. Consideration should be given before prescribing the drug in patients with unknown or negative RET mutation status, as they may have decreased treatment benefit compared to patients with RET mutations.

Excerpts from the vandetanib (Caprelsa) EPAR:

Rearranged during transfection (RET) status
Patients without RET mutation may have a decreased benefit from vandetanib treatment and the benefit/risk balance for this group of patients may therefore differ from that of the group with RET mutations. For patients whose RET mutation status could be negative, a possible lower benefit should be taken into account before individual treatment decisions and the use of vandetanib should be carefully considered because of the treatment related risks. Therefore RET mutation testing is recommended. When establishing RET mutation status, tissue samples should be obtained if possible at the time of initiation of treatment rather than at the time of diagnosis (see sections 4.1 and 5.1).


Vandetanib also inhibits both wild type and the majority of mutated, activated forms of RET, and significantly inhibits the proliferation of MTC cell lines in vitro.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the vandetanib (Caprelsa) EMA drug label.

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

Genes and/or phenotypes found in this label

  • Thyroid Neoplasms
    • Indications & usage section, Information for patients section, efficacy
    • source: European Medicines Agency (EMA) Label
  • CYP3A4
    • Drug interactions section, Pharmacokinetics section, Warnings and precautions section, metabolism/PK
    • source: European Medicines Agency (EMA) Label
  • KDR
    • Pharmacodynamics section, efficacy
    • source: European Medicines Agency (EMA) Label
  • RET
    • Indications & usage section, Clinical studies section, Pharmacodynamics section, Warnings and precautions section, efficacy
    • source: European Medicines Agency (EMA) Label
  • SLC22A2
    • Drug interactions section, metabolism/PK
    • source: European Medicines Agency (EMA) Label

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.

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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?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1799939 1255184G>A, 2071G>A, 42603G>A, 43610119G>A, Gly691Ser
G > A
Missense
Gly691Ser
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  cadherin-related family member 16
Alternate Symbols:  CDHF12; CDHR16; PTC; RET51
PharmGKB Accession Id: PA34335

Details

Cytogenetic Location: chr10 : q11.21 - q11.21
GP mRNA Boundary: chr10 : 43572517 - 43625799
GP Gene Boundary: chr10 : 43562517 - 43628799
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.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Sorafenib Pharmacodynamics
    Mechanism of action of sorafenib

External Pathways

Links to non-PharmGKB pathways.

  1. Signaling events regulated by Ret tyrosine kinase - (Pathway Interaction Database NCI-Nature Curated)

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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
NTRK1

Curated Information ?

Curated Information ?

Publications related to RET: 6

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients. Cancer chemotherapy and pharmacology. 2013. Kim Hye Ryun, 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
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in medicine : official journal of the American College of Medical Genetics. 2013. Green Robert 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
Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients With Medullary Thyroid Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Kurzrock Razelle, 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
Personalized cancer therapy gets closer. Nature. 2009. Hayden Erika Check. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Renal aplasia in humans is associated with RET mutations. American journal of human genetics. 2008. Skinner Michael 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
The consensus coding sequences of human breast and colorectal cancers. Science (New York, N.Y.). 2006. Sjöblom Tobias, et al. PubMed

LinkOuts

HuGE:
RET
Comparative Toxicogenomics Database:
5979
ModBase:
P07949
HumanCyc Gene:
HS09276
HGNC:
9967

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