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Genomics of Pineoblastoma
Source: Childhood Cancer Genomics (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: April 30, 2025 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary. Independent clinical review is pending.
Context: Central Nervous System Tumors / Pineoblastoma
Pineoblastoma, which was previously conventionally grouped with embryonal tumors, is now categorized by the World Health Organization as a pineal parenchymal tumor. Given that therapies for pineoblastoma are quite similar to those used for embryonal tumors, the previous convention of including pineoblastoma with the central nervous system embryonal tumors is followed here. Pineoblastoma is associated with germline pathogenic variants in both the RB1 gene and the DICER1 gene, as described below:
Pineoblastoma is associated with germline pathogenic variants in RB1. The term trilateral retinoblastoma is used to refer to ocular retinoblastoma in combination with a histologically similar brain tumor generally arising in the pineal gland or other midline structures. Historically, intracranial tumors have been reported in 5% to 15% of children with heritable retinoblastoma.[160] Rates of pineoblastoma among children with heritable retinoblastoma who undergo current treatment programs may be lower than these historical estimates.[161-163] In a study of patients with molecularly classified pineal parenchymal tumors, 6 of 221 cases (3%) had a clinical diagnosis of trilateral retinoblastoma.[164]
Germline DICER1 pathogenic variants occur in some patients with pineoblastoma.[165] In one study, among 18 patients with pineoblastoma, 3 patients with DICER1 germline pathogenic variants were identified, and an additional 3 patients known to be carriers of germline DICER1 pathogenic variants developed pineoblastoma.[165] The DICER1 variants in patients with pineoblastoma are loss-of-function variants that appear to be distinct from the variants observed in DICER1 syndrome–related tumors such as pleuropulmonary blastoma.[165]
Genomic methods have been applied to pineoblastoma in an attempt to learn more about the tumor biology and guide future molecular classification. A retrospective, international meta-analysis included 221 children and adults diagnosed with pineoblastoma (n = 178) and pineal parenchymal tumors of intermediate differentiation (PPTID) (n = 43).[164] The evaluation identified four molecular groups of pineoblastoma based on DNA methylation, transcriptome profiling, and gene sequencing, as described below.
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The microRNA (miRNA) processing–altered 1 (PB-miRNA1) and miRNA processing–altered 2 (PB-miRNA2) subtypes are characterized by somatic or germline variants involving miRNA biogenesis genes (DICER1, DROSHA, and DGCR8).
The microRNA (miRNA) processing–altered 1 (PB-miRNA1) and miRNA processing–altered 2 (PB-miRNA2) subtypes are characterized by somatic or germline variants involving miRNA biogenesis genes (DICER1, DROSHA, and DGCR8).
PB-miRNA1 represented approximately 50% of molecularly classified pineoblastoma cases, while PB-miRNA2 represented approximately 15% of the cases.
The microRNA (miRNA) processing–altered 1 (PB-miRNA1) and miRNA processing–altered 2 (PB-miRNA2) subtypes are characterized by somatic or germline variants involving miRNA biogenesis genes (DICER1, DROSHA, and DGCR8).
The median age at presentation of PB-miRNA1 was approximately 8 years, and the median age at presentation of PB-miRNA2 was 12 years.
The microRNA (miRNA) processing–altered 1 (PB-miRNA1) and miRNA processing–altered 2 (PB-miRNA2) subtypes are characterized by somatic or germline variants involving miRNA biogenesis genes (DICER1, DROSHA, and DGCR8).
The 5-year survival rate for patients with PB-miRNA2 (100%) exceeded that for patients with PB-miRNA1 (70%).
The PB-MYC/FOXR2 subtype shows MYC activation (sometimes with MYC copy number gain and occasionally with MYC amplification) and FOXR2 overexpression.
The PB-MYC/FOXR2 subtype shows MYC activation (sometimes with MYC copy number gain and occasionally with MYC amplification) and FOXR2 overexpression.
PB-MYC/FOXR2 represented approximately 20% of molecularly classified pineoblastoma cases.
The PB-MYC/FOXR2 subtype shows MYC activation (sometimes with MYC copy number gain and occasionally with MYC amplification) and FOXR2 overexpression.
PB-MYC/FOXR2 cases presented at a young age (median, 1.4 years).
The PB-MYC/FOXR2 subtype shows MYC activation (sometimes with MYC copy number gain and occasionally with MYC amplification) and FOXR2 overexpression.
Approximately 40% of patients with PB-MYC/FOXR2 presented with metastatic disease.
The PB-MYC/FOXR2 subtype shows MYC activation (sometimes with MYC copy number gain and occasionally with MYC amplification) and FOXR2 overexpression.
The 5-year survival rate for patients with PB-MYC/FOXR2 was approximately 20%.
The PB-RB1 subtype has RB1 alterations. In one study, 6 of 25 patients with the PB-RB1 subtype had a clinical diagnosis of trilateral retinoblastoma.
The PB-RB1 subtype has RB1 alterations. In one study, 6 of 25 patients with the PB-RB1 subtype had a clinical diagnosis of trilateral retinoblastoma.
The PB-RB1 subtype represented approximately 10% of molecularly classified pineoblastoma cases.
The PB-RB1 subtype has RB1 alterations. In one study, 6 of 25 patients with the PB-RB1 subtype had a clinical diagnosis of trilateral retinoblastoma.
Approximately 70% of PB-RB1 cases presented with metastatic disease.
The PB-RB1 subtype has RB1 alterations. In one study, 6 of 25 patients with the PB-RB1 subtype had a clinical diagnosis of trilateral retinoblastoma.
The 5-year survival rate for patients with PB-RB1 was approximately 30%.
Cases with DNA methylation profiles indicating PPTID sometimes had a histological diagnosis of pineoblastoma, but the clinical and biological characteristics of these cases were distinctive from those of the pineoblastoma subtypes described above.
Cases with DNA methylation profiles indicating PPTID sometimes had a histological diagnosis of pineoblastoma, but the clinical and biological characteristics of these cases were distinctive from those of the pineoblastoma subtypes described above.
Approximately 75% of cases with a molecular classification of PPTID had tumors with variants in KBTBD4, a gene that is also altered in group 3 and 4 medulloblastomas.
Cases with DNA methylation profiles indicating PPTID sometimes had a histological diagnosis of pineoblastoma, but the clinical and biological characteristics of these cases were distinctive from those of the pineoblastoma subtypes described above.
Most PPTID cases occurred in adults, with a median age exceeding 30 years.
Cases with DNA methylation profiles indicating PPTID sometimes had a histological diagnosis of pineoblastoma, but the clinical and biological characteristics of these cases were distinctive from those of the pineoblastoma subtypes described above.
The 5-year survival rate for patients with PPTID was 85%.
For information about the treatment of childhood pineoblastoma, see Childhood Medulloblastoma and Other Central Nervous System Embryonal Tumors Treatment.
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