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NUTM1 probe for FISH CE/IVD - Salivary gland cancers
NUT midline carcinoma (NMC) is a rare and aggressive form of squamous cell carcinoma that arises mainly in the head, neck, or mediastinum. NMC is genetically defined by the presence of chromosomal rearrangements involving the NUTM1 gene. Two-thirds of NMCs have t(15;19) (q14;p13.1) fusing the NUTM1 gene to the BRD4 gene. Less commonly, NMC harbors a NUTM1-variant fusion gene involving BRD3 or still-uncharacterized genes. NMCs may be indistinguishable from more common squamous cell carcinomas and are thus an underdiagnosed entity. Therefore, the diagnosis of NMC depends on the confirmation of NUTM1 rearrangement. BRD3 and BRD4 belong to the bromo and extra terminal (BET) family of bromodomain proteins. BRD-NUTM1 chimeric oncoproteins repress squamous differentiation, possibly by sequestering histone acetyltransferase activity. Accordingly, histone deacetylase inhibitors or BET inhibitors were shown to reverse the effects of BRD-NUTM1 fusion proteins by inducing terminal differentiation of NMC cells in vitro and in xenograft models. Hence, detection of NUTM1 rearrangements by FISH represents a useful tool in the differential diagnosis of NMC and may be of therapeutic significance.
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