PNDM is a genetically heterogeneous disorder due to mutations in 23 different genes described to date: KCNJ11, ABCC8, FOXP3, GCK, PDX1, pancreas-specific transcription factor 1A (PTF1A), EIF2AK3, SLC2A2, GATA6, GATA4, SLC19A2, WFS1, NEUROD1, NEUROG3, RFX6, LRBA, NKX2-2
, MNX1, IER3IP1, INS, S T A T 3 , GLIS3 and HNF1B (3,4,5,6,7,8,9).
They also tested the promoter methylation of 33 genes; only PROX1, NNAT, ARHGAP6, HAND2, NKX2-2
, PCDH10, DAPK1, RAB6C, and PITX2 could effectively tell the difference among the various stages of tumor with high sensitivity and specificity .
Although the functional role of some famous transcription factors such as AR, SMAD3 and VDR are well known as genes linked to prostate cancer (40-42), the 9 transcription factors (CAMTA1, ISL1, MNX1, NHLH2, NKX2-2
, STAT2, ZNF146, ZNF205, and ZNF529) are new candidates that may have critical roles in prostate cancer based on topological significance and regulatory changes during cancer progression.
is a transcription factor with a crucial role in differentiation of the central nervous system and pancreatic islets, which has been demonstrated to be expressed in 93% of Ewing sarcomas/primitive neuroectodermal tumors and was not expressed in most of the other small round cell tumors, with exception of olfactory neuroblastomas and a minor subset of small cell carcinomas, synovial sarcomas, mesenchymal chondrosarcomas, and malignant melanomas.
Analysis of transcription factors key for mouse pancreatic development establishes NKX2-2
and MNX1 mutations as causes of neonatal diabetes in man.