Dr. Lu- Cincinnati Children's
We have performed whole genome sequencing of nine pineoblastoma tumors to
identify mutations. Having 9 samples is significantly important due to the rarity of
pineoblastoma. Additionally, our team extracted DNA from the blood samples of
three PB patients and performed whole genome sequencing analysis to identify de
novo mutations in these tumors. We were unable to carry out transcriptomics
profiling of these tumor samples due to low RNA quality. Nonetheless, based on the
whole genome sequencing data, we identified several interesting anomalies in the
samples we tested. Following is a summary of our findings:
1. 12 million variants (mutations + small indels) were identified through alignment of
sequences from WGS experiments of 9 pineoblastoma samples against the
reference genome hg38. 31,162 of the variants were expected to result in
changes in protein sequences or functions.
2. In both the pineoblastoma and blood sample of patient P2, there is a C->T
mutation that led to an A564->V change in the DICER1 protein sequence.
3. In the pineoblastoma sample of patient P5, there is a nonsense mutation at Q301
leading to a truncated DICER1 protein.
4. We also found large sectional losses of chrX and chrY, and a small amplicon on
chr7 (9.5-10.5 Mb) from the DNA copy analysis of patient P8.
Currently, we are conducting cytogenetic analysis to identify genetic mutations and
epigenetic changes that might be responsible for driving the formation of
pineoblastoma tumors. Ultimately, we hope this will lead to identifying the genetic
cause(s) of pineoblastoma. Additionally, we will stratify patients with inconclusive
genetic results from cytogenetic analysis into risk groups based on differing clinical
outcomes.
Furthermore, we have established pineoblastoma (PB) animal models by mutating
Dicer1 and Rb1, recurrent mutations found in patients, and have isolated and
cultured mouse PB tumor cells. We are currently testing various immunotherapy
approaches to target these tumor cells, which may pave the way for future
immunotherapy treatments for pineoblastoma.
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