Ovary: inv(10)(q11q11) in ovarian germ cell tumors

Hybrid Gene
Note	The RET/NCOA4 fusion gene is also referred to as PTC3.
	Diagrammatic representation of RET and NCOA4 exon locations on Chromosome 10. Introns and exons are to scale within respective genes. Breakpoints within each gene are indicated (BP).
Description	The inv(10)(q11q11) results in fusion of exons 1-6 of NCOA4 with exon 12-through to the C-terminus of RET.
Detection	RT-PCR, Southern blot, and FISH (see Zu et al., 2006 for detailed methods).
Fusion Protein
Note	The RET/NCOA4 fusion protein is also referred to as PTC3. Chimeric protein consisting of the tyrosine kinase domain of RET fused downstream of the homodimerization domain of NCOA4. Constitutive dimerization of fusion proteins results in continuous downstream signalling through canonical cell growth and proliferation pathways, promoting oncogenesis.
Description	Diagrammatic representation of RET/NCOA4 (PTC3) fusion protein. Amino acids surrounding each breakpoint (arrows) are indicated, and numbered according to their position within RET or NCOA4, respectively. Peptide sequences from RET are in red, from NCOA4 in green. The transmembrane domain (TM) of RET is shown in yellow. IC - intracellular domain.
Description	Fusion protein consists of amino acids 1-238 of NCOA4 and 712-C-terminus of RET. The N-terminal region donated by NCOA4 contains a homodimerization domain that results in constitutive dimerization and activation of the RET kinase domain in the C-terminal region of the molecule. Constitutive activation increases signalling through a number of downstream signalling pathways involved in cell proliferation and survival, promoting oncogenesis.
Expression Localisation	Cytoplasm.
Oncogenesis	RET/NCOA4 fusion proteins have been implicated in the oncogenesis of papillary thyroid carcinoma.

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