Alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) are found in about two thirds of cases in the three core PB subtypes.
Patients with germline mutations in DICER1, a ribonuclease involved in microRNA processing, have increased risk of pineoblastoma, but genetic drivers of sporadic pineoblastoma remain unknown.
The eighteen PinBs were sequenced by Sanger and/or Fluidigm-based next-generation sequencing to identify DICER1 mutations in blood gDNA and/or tumour gDNA.
The proportions of HIOMT-immunoreactive cells successively decreased in the following tumors: pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma.
The pineocytomas showed high expression of TPH, HIOMT, and genes related to phototransduction in the retina (OPN4, RGS16, and CRB3), whereas the pineoblastoma showed high expression of UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, and HOXD13.
In the northern blot analysis, an apparently single band corresponding to the size of HIOMT mRNA was detected in both pineoblastoma and pineocytoma RNA blots.
This study suggests that germ-line DICER1 mutations make a clinically significant contribution to PinB, establishing DICER1 as an important susceptibility gene for PinB and demonstrates PinB to be a manifestation of a germ-line DICER1 mutation.
Loss of INI1 is a common event in ATRT; therefore, we investigated if the loss of INI1 protein expression was also observed in central nervous system (CNS) PNET and pineoblastoma.
They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma.
The pineocytomas showed high expression of TPH, HIOMT, and genes related to phototransduction in the retina (OPN4, RGS16, and CRB3), whereas the pineoblastoma showed high expression of UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, and HOXD13.
The pineocytomas showed high expression of TPH, HIOMT, and genes related to phototransduction in the retina (OPN4, RGS16, and CRB3), whereas the pineoblastoma showed high expression of UBEC2, SOX4, TERT, TEP1, PRAME, CD24, POU4F2, and HOXD13.
In contrast, all cPNET and other blastic CNS tumors were negative forMIC2: medulloblastoma (0/3), cerebral PNET (0/2), spinal PNET (0/2), glioblastoma (0/2), retinoblastoma (0/3), and pineoblastoma (0/2).