Medullary thyroid carcinoma

Familial Medullary Thyroid Cancer (FMTC) is characterised by the presence of medullary thyroid cancer (MTC) in the absence of phaeochromocytoma or parathyroid adenoma/hyperplasia.  Variants in exons 5, 8, 10, 11, 13, 14, 15 and 16 of the RET gene have been identified in >95% FMTC cases (Hansford and Mulligan 2000 J Med Genet 37:817-827).

Sporadic MTC is defined by the absence of a familial history of MTC and other MEN2A-related tumours.  Approximately 7% patients with presumed sporadic medullary thyroid cancer actually have a germline variant (Romei et al 2011 Clin Endocrinol 74:241-247).  For patients where no germline RET variant has been identified, analysis of the RET and RAS genes can be undertaken in tumour tissue. Somatic RET variants are identified in 35-50% of sporadic MTC tumours, with the p.M918T variant being the most common.  Up to 45% sporadic tumours harbour HRAS, NRAS or KRAS variants.  RET and RAS variants are mutually exclusive (Boichard et al 2012 J Clin Endocrinol Metab 97: E2031–E2035). The presence of a somatic RET variant is a strong negative prognostic marker for overall and disease-free survival (Elisei et al 2008 J Clin Endocrinol Metab 93:682-687), whereas patients with somatic RAS variants have been shown to have a less aggressive tumour phenotype (Ciampi et al 2013 Thyroid 23:50-57).

RET gene analysis in familial medullary thyroid carcinoma & analysis of RET AND RAS genes in sporadic medullary thyroid carcinoma.

Visit the NHS Genomic Test Directory 

Eligibility criteria for genomic tests can be found in the National Genomic Test Directory.

This lists the clinical specialties that would be expected to request for a given clinical indication and sets out which patients should be considered for testing.

All samples for genomic testing should be accompanied by a fully completed request form.

The request form should include as much clinical information about the patient or family member, family relationships and the requested test code (R number). All request forms must indicate either a specific disorder/gene(s) to be investigated or, a request to extract and store DNA.

This form should be used for the majority of test requests.

Please do not download and store this on your desktop or system. The form is regularly updated. Our recommendation is to save or bookmark a link to our website to ensure you are working with the most up-do-date version.

Download the latest version here: GMS Test Order Form v2.3

An appropriate discussion of genomic testing and the possible implications for a patient and their family members must take place before testing is requested.

It is the referring clinician’s responsibility to ensure that the patient/carer knows the purpose of the test and that the sample may be stored for future diagnostic testing. In submitting a sample with a request form, the clinician confirms that informed consent has been obtained for (a) testing and storage (indefinitely) (b) the use of this sample and the information generated from it to be shared with members of the donor’s family and their health professionals (if appropriate). The patient should be advised that the samples may be used anonymously for quality assurance and training purposes.

If stated as a requirement for a specific test, a record of this discussion must be retained within the patient record when a genomic test is ordered.

For more information please view the Consent and Confidentiality in Genomic Medicine guidelines from the Joint Committee on Medical Genetics.

Before sending samples for genomic testing, please ensure you follow the correct preparation and transport guidelines. This includes information on sample types, volumes, handling, labelling, and packaging standards.

For a full list of sample requirements and transport guidance, please visit the samples and transport page of the website. 

Turnaround times (TATs) for genomic tests are continually refined through ongoing reviews of testing standards.

Results will be returned to the email account or clinician listed on the request form.

Visit the results and turnaround page for more information.

AMEND is a registered charity offering support for patients with MEN types 1 and 2, and associated sporadic growths.  Click here to view their website.