Details of Disease

Disease Name

Medullary thyroid gland carcinoma

thyroid carcinoma, medullary; medullary thyroid cancer (MTC); THME; thyroid cancer, medullary; medullary carcinoma; medullary thyroid cancer; thyroid gland medullary cancer; medullary thyroid gland carcinoma; carcinoma of parafollicular cell; carcinoma, C-cell, malignant; ultimobranchial thyroid tumor; MTC; medullary carcinoma of thyroid; thyroid gland medullary carcinoma; thyroid gland neuroendocrine carcinoma; medullary carcinoma of the thyroid gland; parafollicular cell carcinoma; medullary carcinoma of the thyroid; medullary carcinoma of thyroid gland; medullary thyroid carcinoma; thyroid medullary carcinoma; ultimobranchial thyroid tumour; C cell carcinoma

Definition

A neuroendocrine carcinoma arising from the C-cells of the thyroid gland. It is closely associated with multiple endocrine neoplasia syndromes. Approximately 10% to 20% of medullary thyroid carcinomas are familial. Patients usually present with a thyroid nodule that is painless and firm. In the majority of cases nodal involvement is present at diagnosis. Surgery is the preferred treatment for both primary lesions and recurrences. This carcinoma is generally not very sensitive to radiation and almost unresponsive to chemotherapy.

Disease Hierarchy

DISVGJET: Neuroendocrine cancer

DISH9F1N: Carcinoma

DISFK2QT: Thyroid gland follicular carcinoma

DISHBL3K: Medullary thyroid gland carcinoma

Disease Identifiers

MONDO ID

MONDO_0015277

MESH ID

C536914

UMLS CUI

C0238462

MedGen ID

66772

HPO ID

HP:0002865

Orphanet ID

1332

SNOMED CT ID

255032005

General Information of Disease (ID: DISHBL3K)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Cabozantinib	DMIYDT4	Approved	Small molecular drug	[1]
Sorafenib	DMS8IFC	Approved	Small molecular drug	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 30 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CEACAM5	TTY6DTE	Limited	Biomarker	[3]
S100A12	TTQ4ESF	Limited	Biomarker	[4]
SST	TTWF7UG	Limited	Biomarker	[5]
TK1	TTP3QRF	Limited	Altered Expression	[6]
MAPKAP1	TTWDKCL	moderate	Altered Expression	[7]
ATF4	TTQCKWT	Strong	Biomarker	[8]
CALCB	TTUZ9GV	Strong	Altered Expression	[9]
CALCR	TTLWS2O	Strong	Altered Expression	[10]
CCKBR	TTVFO0U	Strong	Biomarker	[11]
EML4	TT92GY4	Strong	Biomarker	[12]
F9	TTFEZ5Q	Strong	Biomarker	[13]
FLT4	TTDCBX5	Strong	Genetic Variation	[14]
GFRA3	TT63XRS	Strong	Genetic Variation	[15]
GLP1R	TTVIMDE	Strong	Genetic Variation	[16]
HSPA9	TTMTPG3	Strong	Biomarker	[17]
NODAL	TTK2O1Q	Strong	Biomarker	[18]
NTRK1	TTTDVOJ	Strong	Biomarker	[19]
P2RY13	TT1FE3L	Strong	Biomarker	[20]
PPP3CA	TTA4LDE	Strong	Genetic Variation	[21]
PPY	TTIB95A	Strong	Biomarker	[22]
RXFP1	TTMAHD1	Strong	Altered Expression	[23]
SCARB1	TTRE324	Strong	Genetic Variation	[24]
SLC5A5	TTW7HI9	Strong	Altered Expression	[25]
SMYD3	TTKLJYX	Strong	Altered Expression	[26]
SPRY1	TT0PSN6	Strong	Biomarker	[27]
SSTR1	TTIND6G	Strong	Biomarker	[28]
SSTR2	TTZ6T9E	Strong	Altered Expression	[29]
SSTR5	TT2BC4G	Strong	Biomarker	[29]
TSHR	TT6NYJA	Strong	Genetic Variation	[30]
CEACAM3	TTPX7I5	Definitive	Biomarker	[31]
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⏷ Show the Full List of 30 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC31A2	DT8Q56F	Strong	Altered Expression	[32]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MT1A	DE5ME8A	Limited	Biomarker	[19]
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This Disease Is Related to 56 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CHGA	OTXYX5JH	Limited	Altered Expression	[33]
HNRNPA3	OT4O4NFS	Limited	Genetic Variation	[34]
NTM	OTHF0UQU	Limited	Biomarker	[35]
PSG5	OTHTU98X	Limited	Genetic Variation	[36]
SEC23A	OTBRNIJ3	Limited	Altered Expression	[37]
MAP1LC3A	OTPMGIU4	moderate	Altered Expression	[38]
AGBL2	OTCX9987	Strong	Biomarker	[39]
ASCL1	OTI4X44G	Strong	Altered Expression	[40]
BLCAP	OTGJVU0C	Strong	Biomarker	[41]
CCDC6	OTXRQDYG	Strong	Biomarker	[13]
CHP1	OTHTXN1A	Strong	Biomarker	[42]
DCTN3	OTQOSUES	Strong	Biomarker	[42]
DERL2	OTI3TUUZ	Strong	Biomarker	[43]
DOCK11	OTFSTN6A	Strong	Genetic Variation	[44]
DYNC1H1	OTD1KRKO	Strong	Biomarker	[42]
GCHFR	OTEOT8GI	Strong	Altered Expression	[45]
GDF1	OTZ1VRBH	Strong	Genetic Variation	[46]
GFRA1	OT3WBVYB	Strong	Genetic Variation	[47]
GIT1	OTHO92S5	Strong	Biomarker	[48]
HABP2	OTAUIPW0	Strong	Genetic Variation	[49]
INSL3	OT7KUNTE	Strong	Biomarker	[23]
INSM1	OTG8RV8E	Strong	Biomarker	[50]
KIF5B	OTT34MT8	Strong	Genetic Variation	[51]
KLF9	OTBFEJRQ	Strong	Biomarker	[8]
MAP1LC3B	OTUYHB84	Strong	Altered Expression	[38]
MEA1	OT72PHSG	Strong	Genetic Variation	[52]
MEN1	OTN6U6V0	Strong	Altered Expression	[53]
MOS	OTNMQPFJ	Strong	Biomarker	[54]
NANOS2	OTFM2IDJ	Strong	Biomarker	[55]
NKX2-1	OTCMEJTA	Strong	Biomarker	[56]
PAX8	OTRPD9MI	Strong	Genetic Variation	[30]
PAX9	OT25J0F7	Strong	Altered Expression	[57]
PDCD5	OT6T2DDL	Strong	Altered Expression	[58]
PHB2	OTCAX3AW	Strong	Biomarker	[42]
PMPCA	OT5X1G9Q	Strong	Genetic Variation	[24]
PPP1R13L	OTNCPLWE	Strong	Genetic Variation	[46]
PROX1	OT68R6IO	Strong	Altered Expression	[33]
PTPRF	OTH5KF2D	Strong	Biomarker	[59]
PTTG1	OTIMYS4W	Strong	Altered Expression	[60]
RASA2	OTL06RG2	Strong	Biomarker	[61]
RBP3	OTIWM4GT	Strong	Biomarker	[62]
RNF139	OT0PR1X5	Strong	Genetic Variation	[63]
RNH1	OT6EC79B	Strong	Genetic Variation	[46]
RPIA	OT805SMH	Strong	Biomarker	[64]
RREB1	OT62460U	Strong	Biomarker	[65]
RXFP2	OT7SAT9U	Strong	Altered Expression	[23]
SDHC	OTC8G2MX	Strong	Biomarker	[66]
SHC3	OT305NPA	Strong	Genetic Variation	[46]
SYP	OTFJKMO4	Strong	Altered Expression	[67]
TAS2R38	OTX5MM36	Strong	Biomarker	[13]
TG	OT3ELHIJ	Strong	Biomarker	[68]
TMEM11	OTL9HDEY	Strong	Genetic Variation	[69]
TTF1	OT4K90WD	Strong	Biomarker	[56]
CEACAM7	OTKFDTZY	Definitive	Biomarker	[31]
LRIG1	OTY5HZN5	Definitive	Altered Expression	[70]
PSG2	OT2EIXAI	Definitive	Biomarker	[31]
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⏷ Show the Full List of 56 DOT(s)

References

1	Cabozantinib FDA Label
2	Sorafenib FDA Label
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4	Measurement of calcitonin and calcitonin gene-related peptide mRNA refines the management of patients with medullary thyroid cancer and may replace calcitonin-stimulation tests.Thyroid. 2013 Mar;23(3):308-16. doi: 10.1089/thy.2012.0361.
5	Clinical utility of (177) Lu-DOTATATE PRRT in somatostatin receptor-positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity.Head Neck. 2020 Mar;42(3):401-416. doi: 10.1002/hed.26024. Epub 2019 Nov 22.
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7	SIN1, a critical component of the mTOR-Rictor complex, is overexpressed and associated with AKT activation in medullary and aggressive papillary thyroid carcinomas.Surgery. 2014 Dec;156(6):1542-8; discussion 1548-9. doi: 10.1016/j.surg.2014.08.095. Epub 2014 Nov 11.
8	Combinations of Tyrosine Kinase Inhibitor and ERAD Inhibitor Promote Oxidative Stress-Induced Apoptosis through ATF4 and KLF9 in Medullary Thyroid Cancer.Mol Cancer Res. 2019 Mar;17(3):751-760. doi: 10.1158/1541-7786.MCR-18-0354. Epub 2018 Dec 14.
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11	Targeting of the Cholecystokinin-2 Receptor with the Minigastrin Analog (177)Lu-DOTA-PP-F11N: Does the Use of Protease Inhibitors Further Improve In Vivo Distribution?.J Nucl Med. 2019 Mar;60(3):393-399. doi: 10.2967/jnumed.118.207845. Epub 2018 Jul 12.
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24	The RET C611Y mutation causes MEN 2A and associated cutaneous.Endocr Connect. 2018 Sep 1;7(9):998-1005. doi: 10.1530/EC-18-0220.
25	Molecular imaging of advanced thyroid cancer: iodinated radiotracers and beyond.Med Oncol. 2017 Oct 30;34(12):189. doi: 10.1007/s12032-017-1051-x.
26	Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours.Mol Cell Endocrinol. 2014 Jul 5;392(1-2):8-13. doi: 10.1016/j.mce.2014.04.016. Epub 2014 May 9.
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29	Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT.Horm Metab Res. 2002 May;34(5):229-33. doi: 10.1055/s-2002-32134.
30	Intragenic mutations in thyroid cancer.Endocrinol Metab Clin North Am. 2008 Jun;37(2):333-62, viii. doi: 10.1016/j.ecl.2008.02.004.
31	Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review.BMC Endocr Disord. 2019 Oct 16;19(1):103. doi: 10.1186/s12902-019-0435-7.
32	Calcitonin receptor mRNA is expressed in human medullary thyroid carcinoma.Thyroid. 1998 Feb;8(2):141-7. doi: 10.1089/thy.1998.8.141.
33	Expression of Prox1 in Medullary Thyroid Carcinoma Is Associated with Chromogranin A and Calcitonin Expression and with Ki67 Proliferative Index, but Not with Prognosis.Endocr Pathol. 2019 Jun;30(2):138-145. doi: 10.1007/s12022-019-9576-5.
34	A 1.5-megabase yeast artificial chromosome contig from human chromosome 10q11.2 connecting three genetic loci (RET, D10S94, and D10S102) closely linked to the MEN2A locus.Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):492-6. doi: 10.1073/pnas.90.2.492.
35	Differential detection of tuberculous and non-tuberculous mycobacteria by qPCR in lavage fluids of tuberculosis-suspicious white rhinoceros.PLoS One. 2018 Nov 28;13(11):e0207365. doi: 10.1371/journal.pone.0207365. eCollection 2018.
36	Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations.World J Surg. 2002 Aug;26(8):1023-8. doi: 10.1007/s00268-002-6665-1. Epub 2002 May 21.
37	MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.Oncotarget. 2016 May 24;7(21):30461-78. doi: 10.18632/oncotarget.8458.
38	Expression of Autophagy-Related Proteins in Different Types of Thyroid Cancer.Int J Mol Sci. 2017 Mar 2;18(3):540. doi: 10.3390/ijms18030540.
39	Specific immunostaining for CCP II, a novel calcitonin carboxyl terminal peptide encoded by the calcitonin/CGRP gene.J Histochem Cytochem. 1993 Nov;41(11):1605-10. doi: 10.1177/41.11.7691931.
40	Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells.J Biol Chem. 2006 Dec 29;281(52):39819-30. doi: 10.1074/jbc.M603578200. Epub 2006 Nov 7.
41	Upregulated miR-9-3p Promotes Cell Growth and Inhibits Apoptosis in Medullary Thyroid Carcinoma by Targeting BLCAP.Oncol Res. 2017 Sep 21;25(8):1215-1222. doi: 10.3727/096504016X14791715355957. Epub 2016 Nov 17.
42	Site-directed chromosome rearrangements in skin fibroblasts from persons carrying genes for hereditary neoplasms.Cancer Res. 1980 Dec;40(12):4796-803.
43	Coexistent familial nonmultiple endocrine neoplasia medullary thyroid carcinoma and papillary thyroid carcinoma associated with RET polymorphism.Am J Med Sci. 2010 Jul;340(1):60-3. doi: 10.1097/MAJ.0b013e3181dfb245.
44	A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis.Cancer Detect Prev. 1998;22(6):544-8. doi: 10.1046/j.1525-1500.1998.00066.x.
45	Cdk5 regulates STAT3 activation and cell proliferation in medullary thyroid carcinoma cells.J Biol Chem. 2007 Feb 2;282(5):2776-84. doi: 10.1074/jbc.M607234200. Epub 2006 Dec 4.
46	Primary Adrenal Insufficiency During Lenvatinib or Vandetanib and Improvement of Fatigue After Cortisone Acetate Therapy.J Clin Endocrinol Metab. 2019 Mar 1;104(3):779-784. doi: 10.1210/jc.2018-01836.
47	Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma.Oncogene. 2001 Apr 19;20(17):2161-70. doi: 10.1038/sj.onc.1204289.
48	miR-149-5p inhibits cell proliferation and invasion through targeting GIT1 in medullary thyroid carcinoma.Oncol Lett. 2019 Jan;17(1):372-378. doi: 10.3892/ol.2018.9628. Epub 2018 Oct 26.
49	HABP2 Gene Mutations Do Not Cause Familial or Sporadic Non-Medullary Thyroid Cancer in a Highly Inbred Middle Eastern Population.Thyroid. 2016 May;26(5):667-71. doi: 10.1089/thy.2015.0537. Epub 2016 Apr 8.
50	INSM1 is a Sensitive and Specific Marker of Neuroendocrine Differentiation in Head and Neck Tumors.Am J Surg Pathol. 2018 May;42(5):665-671. doi: 10.1097/PAS.0000000000001037.
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59	The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer: a single-center, open-label, phase II, proof-of-concept study.Endocrine. 2018 Oct;62(1):46-56. doi: 10.1007/s12020-018-1583-7. Epub 2018 Mar 23.
60	Novel Prognostic Factors Associated with Cell Cycle Control in Sporadic Medullary Thyroid Cancer Patients.Int J Endocrinol. 2019 Feb 18;2019:9421079. doi: 10.1155/2019/9421079. eCollection 2019.
61	Two GEO MicroRNA Expression Profile Based High-Throughput Screen to Identify MicroRNA-31-3p Regulating Growth of Medullary Thyroid Carcinoma Cell by Targeting RASA2.Med Sci Monit. 2019 Jul 12;25:5170-5180. doi: 10.12659/MSM.916815.
62	The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10.Am J Hum Genet. 1990 Dec;47(6):946-51.
63	The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway.Oncogene. 2002 May 16;21(22):3507-16. doi: 10.1038/sj.onc.1205437.
64	Apoptotic cell death induction and angiogenesis inhibition in large established medullary thyroid carcinoma xenografts by Ret inhibitor RPI-1.Biochem Pharmacol. 2006 Aug 14;72(4):405-14. doi: 10.1016/j.bcp.2006.05.002. Epub 2006 Jun 6.
65	RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.Mol Cell Biol. 1996 Oct;16(10):5335-45. doi: 10.1128/MCB.16.10.5335.
66	No mutations but an increased frequency of SDHx polymorphisms in patients with sporadic and familial medullary thyroid carcinoma.Endocr Relat Cancer. 2005 Dec;12(4):1011-6. doi: 10.1677/erc.1.00996.
67	A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis.Endocr Relat Cancer. 2007 Jun;14(2):433-44. doi: 10.1677/ERC-06-0033.
68	Serum calcitonin negative mixed medullary-follicular carcinoma initially diagnosed as medullary thyroid carcinoma by fine-needle aspiration cytology: A case report and review of the literatures.Diagn Cytopathol. 2018 Aug;46(8):690-693. doi: 10.1002/dc.23924. Epub 2018 Mar 10.
69	Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B.Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1579-83. doi: 10.1073/pnas.91.4.1579.
70	LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer.Int J Oncol. 2018 Apr;52(4):1189-1197. doi: 10.3892/ijo.2018.4273. Epub 2018 Feb 9.