Translocation analysis t(11;19) (q21;p13) (CRTC1-MAML2) is, together with translocation t(11;15)(q21;q26) (CRTC3-MAML2), a typical feature of mucoepidermoid carcinoma (MEC) which is one of the most frequent malignant tumors of the salivary glands. Besides that, the product of this fusion was also found in Warthin's tumors and in clear cell hidradenoma of the skin.
In this translocation there occurs a break in intron 1 of the gene CRTC1 (also MECT1, TORC1 and WAMPT1) which is located on the chromosome 19 and in intron 1 of the gene MALM2 (Mastermind-like 2) which lies on the chromosome 11. This breakage results in the formation of a fusion gene which is composed of exon 1 of the gene MECT1 and exon 2 to 5 of the gene MALM2.
Protein encoded by the gene CRTC1 belongs to the family of highly conservative CREC (cAMP response element-binding) coactivators. CRTC1 increases the transcription from CRE (cAMP response element) through the interaction with bZIP (the basic-leucine zipper) CREB domain.
The product of the gene MALM2 is a transcriptional coactivator in the Notch signaling pathway. Protein MALM2 forms a complex with the intracellular domain of the Notch protein and with proteins from the CLS family of transcription factors. This interaction leads to the activation of Notch downstreem genes, such as HES1 and HES5.
Fusion protein CRTC1/MAML2 has N - terminal basic domain of the gene MAML2 replaced by CREB-binding domain of the gene CRTC1. The molecular consequence of this replacement are not fully understood but hitherto findings suggest that the fusion protein, independently of the input signals, activates CREB dependent genes and Notch signaling pathway as well. Activation of two independent pathways, especially CREB, then probably significantly contributes to an actual neoplastic process.
According to some recent studies, patients with MEC carrying this translocation or sister translocation CRTC3-MAML2 have better "disease free" and "overall survival" than patients without these translocations.
Test is possible to perform from RNA isolated from unfixed and fixed tissues.
The translocation t(11;19) (q21;p13) (CRTC1-MAML2) is detected in analyzed samples using two-round RT-PCR and agarose gel electrophoresis (fig. 1) with possible confirmation of fusion products by sequencing.
We detect also the break of the gene MALM2 using break apart FISH probe.
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