Human Disease Model Report: thyroid carcinoma, nonmedullary, NCOA4-RET fusion

General Information

Name

thyroid carcinoma, nonmedullary, NCOA4-RET fusion

FlyBase ID

FBhh0000662

Disease Ontology Term

papillary thyroid carcinoma

Parent Disease

thyroid carcinoma, nonmedullary

OMIM

Overview

This report describes work assessing an NCOA4-RET fusion. Two RET fusion variants, CCDC6-RET and NCOA4-RET, account for >90% of fusions associated with nonmedullary thyroid carcinoma (NMTC); NCOA4-RET fusions are also observed in other cancers, including lung adenocarcinomas (a subtype of non-small-cell lung cancer). RET encodes a cellular tyrosine kinase transmembrane receptor; activation of RET stimulates multiple downstream pathways that promote cell growth, proliferation, survival and differentiation. NCOA4 encodes an androgen receptor coactivator; the NCOA4-RET fusion is associated with an aggressive NMTC subtype.

A UAS construct incorporating a fusion of the two human genes, indicated in FlyBase as Hsap\NCOA4::Hsap\RET, was introduced into flies. Different aspects of the functional impact of the fusion were assessed using different GAL4 drivers; broad expression results in lethality. Genetic interactions and sensitivity to clinically relevant drugs were tested. A critical finding was that the CCDC6-RET and NCOA4-RET fusions differed in these assays. (See the human disease model report 'thyroid carcinoma, nonmedullary, CCDC6-RET fusion,' FBhh0000661.)

[updated Nov. 2017 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: thyroid carcinoma, nonmedullary

Symptoms and phenotype

Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. Papillary thyroid cancer (PTC) is the most common histologic subtype (summary by Vriens et al., 2009; pubmed:20001717). PTCs smaller than 1 cm are referred to as papillary microcarcinomas; these tumors have been identified in up to 35% of individuals at autopsy, suggesting that they may be extremely common, although rarely clinically relevant (summary by Bonora et al., 2010; pubmed:20628519). [from MIM:188550; 2017.11.24]

(OMIM, 2013-)

Specific Disease Summary: thyroid carcinoma, nonmedullary, NCOA4-RET fusion

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Two RET fusion isoforms, CCDC6-RET and NCOA4-RET, account for >90% of fusions associated with nonmedullary thyroid carcinoma; NCOA4-RET is associated with a more aggressive and malignant subtype (FBrf0233455).

(FlyBase Curators, 2013-)

Cellular phenotype and pathology

RET fusion proteins are not localized to the cell membrane (FBrf0233455).

(FlyBase Curators, 2013-)

Molecular information

RET (rearranged during transfection proto-oncogene) encodes a cellular tyrosine kinase transmembrane receptor. Activation of RET stimulates multiple downstream pathways that promote cell growth, proliferation, survival and differentiation. These pathways include the mitogen-activated protein kinase (MAPK), the phosphoinositide 3-kinase (PI3K) and protein kinase B, signal transducer and activator of transcription 3, proto-oncogene tyrosine-protein kinase Src1 and focal adhesion kinase pathways (Romei et al., 2016; pubmed:26868437).

(FlyBase Curators, 2013-)

Nuclear receptor coactivator 4 (NCOA4) encodes an androgen receptor coactivator; it interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. [Gene Cards, NCOA4; 2017.11.27]

(FlyBase Curators, 2013-)

External links