(208) Fluorescence in situ hybridization probes targeting 13 of these regions were developed and tested against a cohort of nevi and melanomas, eventually yielding a final probe set targeting 6p25 (RREB1
), 6q23 (MYB), and 11q13 (CCND1) (as well as a probe against centromere 6).
The SSC7 g.4937240C>G marker obtained from the primer combination E-AGC/T-CCA was located at position 4.93 Mb on porcine chromosome 7 close to the porcine ras responsive element binding protein 1 (RREB1
, 4.59 Mb) gene.
Ng et al., "The ras responsive transcription factor RREB1
is a novel candidate gene for type 2 diabetes associated end-stage kidney disease," Human Molecular Genetics, vol.
Among the regions identified by the international research team are two, near the genes ARL15 and RREB1
, that also show strong links to elevated levels of insulin and glucose in the body - two key characteristics of type 2 diabetes.
ATF6 AACS 1.198925 MYCN AAGAB 1.031 DDIT3 AAMP 1.237609 RREB1
AAMP 1.005331 STAT2 AAMP 1.085082 STAT3 AAMP 1.268363 STAT4 AAMP 1.067587 CBFB AASS 1.027421 NFYA AASS 1.028667 ARNT AATF 1.000478 TABLE 2: Top 10 TFs in differentially regulatory network.
The repressor factor RREB1
(Ras Responsive Element Binding 1) may also be implicated in HLA-G expression regulation.
Genetic loci included in most commercially available FISH assays target the chromosomal loci 6p25 (RREB1
), 6q23 (MYB), 8q24 (MYC), 9p21 (CDKN2A), and 11q13 (CCND1).
When using a 4-probe FISH panel evaluating loci commonly altered in melanoma--MYB (6q23), RREB1
(6p25), CCND1 (11q13), and centromere 6 (Cep6)--studies have found high sensitivity and specificity when distinguishing unequivocal nevi from melanoma.
Single-nucleotide polymorphism array interrogation identified copy number changes, including gains at 6p25 (RREB1
) and 11q13 (CCND1; Figure 2, C, and Supplemental Table S1; see supplemental material file at www.archivesofpathology.org in the October 2014 table of contents), both of which are frequent sites of copy gain in melanoma.
(507-509) For example, a combination of probes against 6p25 (RREB1
), 6q23 (MYB), 11q13 (CCND1), and the centromeric region of chromosome 6 was reported to have a sensitivity of 83% and a specificity of 94% when compared to common nevi, dysplastic nevi, and Spitz nevi, with a 6p25 probe showing the highest specificity overall.
(4) The FISH probes used in this assay target ras responsive element binding protein 1 (RREB1
, 6p25), myeloblastosis viral oncogene homolog (MYB, 6q23), Cen6 (centromere 6) and cyclin D1 (CCND1, 11q13) loci.
A commercially available FISH panel for the diagnosis of melanoma contains 4 probes directed against 2 chromosomes (6p25 RREB1
, 6q23 MYB, 6centromere, 11q13 CCND1).