Human Disease Model Report: thyroid carcinoma, familial medullary

General Information

Name

thyroid carcinoma, familial medullary

FlyBase ID

FBhh0000025

Disease Ontology Term

familial medullary thyroid carcinoma

Parent Disease

OMIM

THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC

Overview

Medullary thyroid carcinoma (MTC) occurs sporadically (~75%) or as a component of the multiple endocrine neoplasia (MEN) type 2; see reports for multiple endocrine neoplasia, type IIA (FBhh0000013) and multiple endocrine neoplasia, type IIB (FBhh0000014). There are two human genes implicated in this disease, RET (MIM:164761) and NTRK1 (MIM:191315), both of which are implicated in other diseases, as well. There is a single fly ortholog, Dmel\Ret, of RET; there is no gene with significant orthology to NTRK1 in Drosophila.

Variant(s) implicated in human disease tested (as analogous mutation in fly gene): M955T in the fly Ret gene (corresponds to M918T in the human RET gene); this variant is implicated in MEN2B.

[updated Oct. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: thyroid carcinoma, familial medullary

OMIM report

[THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC](https://omim.org/entry/155240)

Human gene(s) implicated

[RET PROTOONCOGENE; RET](https://omim.org/entry/164761)

Symptoms and phenotype

For additional information on classification and genetics see http://www.thyroidcancer.com/thyroid-cancer/medullary/genetics.

(FlyBase Curators, 2013-)

Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin-secreting parafollicular C cells of the thyroid; it can occur sporadically or as a component of multiple endocrine neoplasia (MEN) type 2 [from MIM:155240; 2015.02.17].

(OMIM, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

External links

COSMIC gene: RET
Gene2Function (human gene): RET
Gene Cards: RET
MedlinePlus (gene): RET
KEGG Disease Pathways: Thyroid cancer
MARRVEL (human gene): RET
NCBI MedGen: Familial medullary thyroid carcinoma (FMTC)
NCBI (Entrez) gene: RET; ret proto-oncogene

Disease synonyms

FMTC

MTC

MTC1

Search term: thyroid cancer

Related Diseases

Related human health report(s)

cancer, general (fly models overview)

multiple endocrine neoplasia, type IIA

multiple endocrine neoplasia, type IIB

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

RET; ret proto-oncogene

D. melanogaster ortholog (based on DIOPT)

Dmel\Ret

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Ret

Gene Snapshot

Ret oncogene (Ret) encodes a cell surface receptor mediating dendrite development of class IV dendritic arborization sensory neurons. It interacts with integrins and mediates rac1 signaling to promote dendrite adhesion to the extracellular matrix. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (2 groups)

Ret

protein-protein

Interacting group

Assay

References

Ret - Gfrl

pull down, molecular weight estimation by staining, western blot, anti bait coimmunoprecipitation, anti tag western blot

(Myers et al., 2018, Saarenpää et al., 2017)

Ret - mys

anti tag coimmunoprecipitation, anti tag western blot

(Soba et al., 2015)

Alleles Reported to Model Human Disease (Disease Ontology) (12 alleles)

Ret

Models Based on Experimental Evidence ( 8 )

Allele

Disease

Evidence

References

Ret^GMR.PR

model of familial medullary thyroid carcinoma

CEA

(Vidal et al., 2005)

Ret^MEN2A.GMR

model of multiple endocrine neoplasia type 2A

CEA

(Read et al., 2005)

model of familial medullary thyroid carcinoma

CEA

(Vidal et al., 2005)

Ret^MEN2B.GMR

model of multiple endocrine neoplasia type 2B

CEA

(Read et al., 2005)

model of familial medullary thyroid carcinoma

CEA

(Vidal et al., 2005)

Ret^KK107206

model of Hirschsprung's disease

CEA

(Myers et al., 2018)

Ret^LM1

model of Hirschsprung's disease

CEA

(Myers et al., 2018)

Ret^LM2

model of Hirschsprung's disease

CEA

(Myers et al., 2018)

Ret^LM3

model of Hirschsprung's disease

CEA

(Myers et al., 2018)

Ret^MEN2B.UAS

model of cancer

CEA

(Das et al., 2013, Dar et al., 2012)

CEA with Nek2^UAS.GFP

(Das et al., 2013)

model of multiple endocrine neoplasia type 2B

CEA

(Fereres et al., 2019, Sonoshita et al., 2018)

Modifiers Based on Experimental Evidence ( 7 )

Allele

Disease

Interaction

References

Ret^MEN2A.GMR

model of multiple endocrine neoplasia type 2A

is exacerbated by Mi-2^S005504

(Read et al., 2005)

is ameliorated by kis^k10237

(Read et al., 2005)

is ameliorated by S^k09538a

(Read et al., 2005)

is exacerbated by Sin3A^ex4

(Read et al., 2005)

is exacerbated by msn^j1E2

(Read et al., 2005)

is ameliorated by S^IIN

(Read et al., 2005)

is exacerbated by Mi-2^S147412

(Read et al., 2005)

is ameliorated by spi¹

(Read et al., 2005)

is exacerbated by Sin3A⁰⁸²⁶⁹

(Read et al., 2005)

is ameliorated by Ras85D⁰⁶⁶⁷⁷

(Read et al., 2005)

is ameliorated by Delta^S049520

(Read et al., 2005)

is exacerbated by hh^rJ413

(Read et al., 2005)

is ameliorated by Delta^9P

(Read et al., 2005)

is ameliorated by ebi^k16213

(Read et al., 2005)

is ameliorated by spi^s3547

(Read et al., 2005)

is ameliorated by drk¹⁰⁶²⁶

(Read et al., 2005)

is exacerbated by hh²

(Read et al., 2005)

is ameliorated by Fak^UAS.Tag:HA

(Macagno et al., 2014)

Ret^MEN2B.GMR

model of multiple endocrine neoplasia type 2B

is exacerbated by Sin3A^HW52

(Read et al., 2005)

is ameliorated by drk^k02401

(Read et al., 2005)

is ameliorated by drk^k13809

(Read et al., 2005)

is ameliorated by kis^k13416

(Read et al., 2005)

is exacerbated by hh^rJ413

(Read et al., 2005)

is ameliorated by Delta^S049520

(Read et al., 2005)

is ameliorated by S^IIN

(Read et al., 2005)

is exacerbated by Sin3A⁰⁸²⁶⁹

(Read et al., 2005)

is ameliorated by spi⁰¹⁰⁶⁸

(Read et al., 2005)

is ameliorated by S^k09538a

(Read et al., 2005)

is exacerbated by msn⁰³³⁴⁹

(Read et al., 2005)

is exacerbated by Sin3A^k07401

(Read et al., 2005)

is exacerbated by Sin3A^k08919

(Read et al., 2005)

is ameliorated by S^k09530

(Read et al., 2005)

is exacerbated by hh²

(Read et al., 2005)

is ameliorated by hh^neo56

(Read et al., 2005)

is ameliorated by Delta^9P

(Read et al., 2005)

is exacerbated by Mi-2^S147412

(Read et al., 2005)

is ameliorated by ebi^k16213

(Read et al., 2005)

is exacerbated by Mi-2^j3D4

(Read et al., 2005)

is exacerbated by Mi-2^S047526

(Read et al., 2005)

is ameliorated by kis^k16510

(Read et al., 2005)

is ameliorated by drk¹⁰⁶²⁶

(Read et al., 2005)

is ameliorated by spi^s3547

(Read et al., 2005)

is exacerbated by Csk^j1D8

(Read et al., 2005)

is exacerbated by hh^AC

(Read et al., 2005)

is ameliorated by kis^k10237

(Read et al., 2005)

is ameliorated by spi¹

(Read et al., 2005)

is ameliorated by Ras85D⁰⁶⁶⁷⁷

(Read et al., 2005)

is exacerbated by msn^j1E2

(Read et al., 2005)

is exacerbated by Sin3A^ex4

(Read et al., 2005)

is ameliorated by Ras85D^ΔC40B

(Read et al., 2005)

is exacerbated by Mi-2^S005504

(Read et al., 2005)

model of cancer

is exacerbated by Sin3A^KK100700

(Das et al., 2013)

Ret^K805A.UAS

DOES NOT ameliorate neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2013)

Ret^HMC03102

ameliorates lung adenocarcinoma

modeled by Hsap\KIF5B::Hsap\RET^UAS.cDa

(Das and Cagan, 2017)

Ret^MEN2A.UAS

model of multiple endocrine neoplasia type 2A

is exacerbated by Fak^CG1

(Macagno et al., 2014)

is ameliorated by Fak^UAS.Tag:HA

(Macagno et al., 2014)

is exacerbated by Fak^5-SZ-3124

(Macagno et al., 2014)

Ret^MEN2B.UAS

DOES NOT ameliorate Parkinson's disease

modeled by Pink1^B9

(Klein et al., 2014)

ameliorates Parkinson's disease

modeled by Pink1^B9

(Klein et al., 2014)

model of multiple endocrine neoplasia type 2B

is exacerbated by Lk6²

(Sonoshita et al., 2018)

is ameliorated by Lk6^RNAi.UAS.cUa

(Sonoshita et al., 2018)

is ameliorated by Raf⁷

(Sonoshita et al., 2018)

is ameliorated by Irk2^DN.UAS

(Fereres et al., 2019)

is ameliorated by SCAR^GD11380

(Fereres et al., 2019)

is ameliorated by dia^GL00408

(Fereres et al., 2019)

Ret^{UAS.Tag:LOV(VfAU1)}

ameliorates Parkinson's disease 6

modeled by Pink1^B9

(Ingles-Prieto et al., 2021)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Ret^MEN2B.UAS

P{UAS-Ret.MEN2B}

Ret^{UAS.Tag:LOV(VfAU1)}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD45}v843

y¹ v¹; P{TRiP.JF01968}attP2

y¹ v¹; P{TRiP.HMC03102}attP40

Ret^HMC04143

P{TRiP.HMC04143}

y¹ v¹; P{TRiP.HMC04143}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Ret^KO

amorphic allele - molecular evidence

ends-out gene targeting

Ret^LM1

amorphic allele - molecular evidence

CRISPR/Cas9

w^*/Dp(1;Y)y⁺, P{ActGFP}SH1; Ret^LM1

Ret^LM2

amorphic allele - molecular evidence

CRISPR/Cas9

Ret^LM3

amorphic allele - molecular evidence

CRISPR/Cas9

w^*; Ret^LM3/CyO, P{ActGFP}JMR1

References (12)

Report Sections

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