The ZytoLight ® SPEC RET Dual Color Break Apart Probe is designed to detect translocations involving the chromosomal region 10q11.21 harboring the RET (rearranged during transfection proto-oncogene) gene.RET encodes a tyrosine kinase (TK) receptor.
Translocations involving RET were first described in papillary thyroid carcinoma(PTC) where somatic rearrangements result in the fusion of its TK catalytic domain with an N-terminal dimerization domain encoded by various fusion partner genes.More recently, recurrent inversions [inv(10)(p11.2q11.2)] fusing the coiled-coildomains of the kinesin family member 5B(KIF5B) gene to the RET kinase domain have been detected in lung adenocarcinoma.The resulting KIF5B-RET fusion protein can form homodimers through the coiledcoil domains of KIF5B, causing an aberrant activation of the TK of RET, a mechanism known from KIF5B-ALK fusions which is also found in lung adenocarcinoma.Since in vitro studies showed transforming activity of KIF5B-RET which could be suppressed by a TK inhibitor, it was assumed that the chimeric oncogene might be a promising molecular target for the treatment of lung cancer. The same holds true for the very recently discovered BCR-RET and FGFR1OP-RET fusion genes in chronic myelomonocytic leukemia(CMML) generated by two balanced translocations t(10;22)(q11.2;q11.2) and t(6;10)(q27;q11.2), respectively.