Endocrine Cancer: Sequencing Panel
Test Code: 9898
Turnaround time: 5 weeks
Thyroid cancer is divided into several subcategories: (1) differentiated (follicular, papillary and Hurthle); (2) medullary; and (3) anaplastic (aggressive undifferentiated tumor). Medullary thyroid cancer (MTC) develops from the “C” or parafollicular cells of the thyroid gland which produce calcitonin. Approximately 80% of the cases of MTC are sporadic. The remaining inherited syndromes include multiple endocrine neoplasia (MEN) type 2A (also known as MEN 2A), MEN 2B, and familial MTC (FMTC). All three of these subtypes, MEN 2A, MEN 2B and FMTC, are inherited in an autosomal dominant pattern and involve an elevated risk for the development of medullary carcinoma of the thyroid. MEN 2A and MEN 2B have an increased risk for the development of pheochromocytoma. MEN 2A has an elevated risk for parathyroid adenoma or hyperplasia. Additional features in MEN 2B include distinctive facies with enlarged lips, mucosal neuromas of the lips and tongue, and ganglioneuromatosis of the gastrointestinal tract. MTC generally occurs in early childhood in MEN 2B, early adulthood in MEN 2A, and middle age in FMTC.
- American Association of Clinical Endocrinologists. (2001, June). AACE/AAES medical/surgical guidelines for clinical practice: Management of thyroid carcinoma. Available at: http://www.aace.com/clin/guidelines/thyroid_carcinoma.pdf. Accessed on October 5, 2013.
- American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. 2009; 19(6):565-612.
- Moline J, Eng C. GeneReviews™. Multiple Endocrine Neoplasia Type 2. Last updated January 10, 2013. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1257/#men2.REF.americansocietyofclinica.2003.1. Accessed on October 5, 2013.
- Romei C, Cosci B, Renzini G, et al. RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC). Clin Endocrinol (Oxf). 2011; 74(2):241-247.
AIP, CDC73, CDKN1B, MAX, MEN1, PRKAR1A, PTEN, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, VHL
The test is indicated for:
- Individuals with a clinical or suspected diagnosis of endocrine cancer.
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.
Analytical Sensitivity: ~99%.
Submit only 1 of the following specimen types
Type: Whole Blood
Specimen Requirements: In EDTA (purple top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.
Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.
Type: Isolated DNA
Specimen Requirements: In microtainer: 60 μg
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.
Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.
This test is for germline mutation analysis. DNA isolated from FFPE tumor samples is not suitable for this test.
- Hereditary Cancer Syndrome: Sequencing Panel. Endocrine Cancer: Deletion/Duplication Panel.