ZytoLight ® SPEC NUTM1 双色分离探针

The ZytoLight ® SPEC NUTM1 Dual Color
Break Apart Probe is designed to detect
translocations involving the chromosomal
region 15q14 harboring the NUTM1 (NUT
midline carcinoma family member 1, a.k.a.
NUT) gene.
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.