- Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas and primary thyroid sarcomas. Hereditary thyroid cancer can arise from either follicular cells, known as familial non-medullary thyroid cancer (FNMTC), or from calcitonin-producing C cells, known as familial medullary thyroid cancer (FMTC). The latter may be related to multiple endocrine neoplasia (MEN) IIA or IIB or pure FMTC syndromes. Advances in molecular genetics have helped identify the presence of several familial cancer syndromes with FNMTC, usually papillary and follicular cancers.
- Hereditary cancer syndromes are encountered in all medical specialties. Although they account for about 5% of all malignancies. Most hereditary cancers are associated with a “germline mutation” that will be present in every cell of the human body. Identification of patients at risk of inherited cancer susceptibility is dependent upon the ability to characterize genes and alterations associated with increased cancer risk as well as gathering a detailed personal and family history aiding in the identification of the mode of inheritance as well as other family members at risk of suffering from this susceptibility. Most of these genes are inherited in an autosomal dominant fashion.
- The Igenomix Hereditary Thyroid Cancer Precision Panel can be used as a screening and diagnostic tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved, and their high or intermediate penetrance.
The Igenomix Hereditary Thyroid Cancer Precision Panel is indicated in those cases where there is a clinical suspicion of thyroid cancer alongside family history, presenting with the following manifestations:
- Painless, palpable, solitary thyroid nodule
- Parathyroid tumors
- Pancreatic tumors: gastrinoma, insulinoma, glucagonoma etc
- Abdominal pain
- Anterior pituitary tumors: prolactinoma, somatotropinoma
- Visual field defects
- Recurrent hypertension
- Marfanoid phenotype: slender body, long thin extremities, abnormal laxity in joints, pectus excavatum etc
The clinical utility of this panel is:
- The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history suggestive of hereditary thyroid cancer.
- Early initiation of treatment with a multidisciplinary team for appropriate surveillance, surgery, radiation therapy or ablation.
- Risk assessment of asymptomatic family members according to the mode of inheritance
- Reduce morbidity related to thyroid cancer or morbidity secondary to complications of surveillance and treatment.
- Improved pathways from diagnosis to treatment in susceptible population
Genes & Diseases
|GENE||OMIM DISEASES||INHERITANCE*||% GENE COVERAGE (20X)||HGMD**|
|CDKN1A||Multiple Endocrine Neoplasia Type 1||–||100%||2 of 2|
|CDKN1B||Multiple Endocrine Neoplasia Type 1, Multiple Endocrine Neoplasia Type 4||AD||99.99%||19 of 20|
|CDKN2B||Familial Melanoma, Multiple Endocrine Neoplasia Type 1||–||100%||7 of 7|
|CDKN2C||Multiple Endocrine Neoplasia Type 1||–||99.83%||2 of 2|
|FOXE1||Athyreosis, Bamforth-Lazarus Syndrome, Familial Papillary Or Follicular Thyroid Carcinoma, Hypothyroidism, Nonmedullary Thyroid Cancer||AD,AR||84.65%||14 of 22|
|HABP2||Familial Papillary Or Follicular Thyroid Carcinoma, Venous Thromboembolism, Nonmedullary Thyroid Cancer, Nonmedullary||AD||100%||2 of 2|
|HRAS||Bladder Cancer, Costello Syndrome, Epidermal Nevus, Linear Nevus Sebaceus Syndrome, Schimmelpenning-Feuerstein-Mims Syndrome, Nonmedullary Thyroid Cancer||AD||100%||34 of 34|
|MEN1||Familial Isolated Hyperparathyroidism, Insulinoma, Multiple Endocrine Neoplasia Type 1, Pituitary Gigantism, Prolactinoma||AD||99.90%||871 of 876|
|MINPP1||Familial Papillary Or Follicular Thyroid Carcinoma, Nonmedullary Thyroid Cancer||AD||100%||2 of 2|
|NRAS||Colorectal Cancer, Epidermal Nevus, Large Congenital Melanocytic Nevus, linear Nevus Sebaceus Syndrome, Neurocutaneous Melanosis, Noonan Syndrome, RAS-associated Autoimmune Lymphoproliferative Syndrome Type 4, Schimmelpenning-Feuerstein-Mims Syndrome, Nonmedullary Thyroid Cancer||AD||100%||15 of 15|
|RET||Congenital Failure of Autonomic Control, Haddad Syndrome, Hereditary Pheochromocytoma-Paraganglioma, Multiple Endocrine Neoplasia Type 2A, Multiple Endocrine Neoplasia Type 2B, Pheochromocytoma, Renal Agenesis, Sporadic Pheochromocytoma/Secreting Paraganglioma, Familial Medullary Thyroid Carcinoma||AD||100%||453 of 454|
|SRGAP1||Nonmedullary Thyroid Cancer||AD||99.92%||5 of 5|
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
Dralle, H., Machens, A., & Lorenz, K. (2008). Hereditäre Schilddrüsenkarzinome [Hereditary thyroid cancer]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen, 79(11), 1017–1028. https://doi.org/10.1007/s00104-008-1558-y
Guilmette, J., & Nosé, V. (2017). Hereditary and familial thyroid tumours. Histopathology, 72(1), 70-81. doi: 10.1111/his.13373
Accardo, G., Conzo, G., Esposito, D., Gambardella, C., Mazzella, M., Castaldo, F., Di Donna, C., Polistena, A., Avenia, N., Colantuoni, V., Giugliano, D., & Pasquali, D. (2017). Genetics of medullary thyroid cancer: An overview. International journal of surgery (London, England), 41 Suppl 1, S2–S6. https://doi.org/10.1016/j.ijsu.2017.02.064
Haugen, B., Alexander, E., Bible, K., Doherty, G., Mandel, S., & Nikiforov, Y. et al. (2016). 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 26(1), 1-133. doi: 10.1089/thy.2015.0020
NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma. Version l.2016. National Comprehensive Cancer Network. (2021). Retrieved 18 February 2021, from https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf.