Anti-oncogenes of Medulloblastoma (and other cancers) – P53 & PCDH10

August 27, 2013 — Leave a comment

P53 Tumor Suppressor Gene – P53 gene (chromosome 17p13.1) is mutated in some Medulloblastomas. Besides Medulloblastoma, P53 down regulation is also known to contribute to Osteosarcoma, Basal Cell Sarcoma (skin cancer) and Gorlin Syndrome (includes issues like sternum bone deformation).  For those new to this topic, P53 is a gene in every cell in the human body that polices your cells for DNA damage and try’s to stop / repair it. So often if not always in cancer, one or multiple oncogenes will be over expressed driving cancer ( for my son it’s MYC) and anti oncogenes or Tumor Suppressor genes are being suppressed like P53, Since there are dietary supplements that have shown some capability to help turn P53 back up, it seems very worthy to evaluate this avenue if you believe you have P53 being down regulated, particularly if you have the added complications I mentioned that are also specifically linked to P53 chromosome damage.  And since this blog is primarily focused on Viral drivers of cancer, it should be noted that several viruses including CMV are known causes of P53 suppression as well.

http://www.cell.com/abstract/S0092-8674(11)01516-9

http://p53.free.fr/Database/p53_cancer/p53_germline.html

http://www.nature.com/onc/journal/v20/n53/full/1204946a.html

I’ve tried looking into ways to upregulate P53 genes.  Some that I researched include: Silymarin, aka Milk Thistle, as well as Melatonin.
http://mct.aacrjournals.org/content/4/2/207.long

http://www.ncbi.nlm.nih.gov/m/pubmed/22002314/

Another Anti-Oncogene suppressed in Medulloblastoma is PCDH10 located at chromosome 4q28.3 down-regulated in 73% of sampled Medulloblastoma tumor samples.

PCDH10 is a candidate tumor suppressor gene in medulloblastoma.
Hospital for Sick Children, Toronto

The aim of this study was to investigate the genetic and epigenetic mechanisms contributing to PCDH10 down-regulation in medulloblastoma. We examined the role of PCDH10 as a mediator of medulloblastoma cell proliferation, cell cycle progression, and cell migration.

METHODS:
We identified a focal homozygous deletion of PCDH10 in medulloblastoma by surveying a cohort of 212 tumors by Affymetrix SNP array analysis. PCDH10 expression was assessed by quantitative reverse transcriptase PCR in a series of 26 tumors. The promoter methylation status of PCDH10 was determined using methylation specific PCR and Sequenom MassCLEAVE analysis. Functional studies examining the role of PCDH10 in medulloblastoma development were performed by re-expression of PCDH10 in the DAOY medulloblastoma cell line, and then, cell proliferation, cell cycle distribution, and cell migration assays were performed.

RESULTS:
We report a very focal homozygous deletion on chromosome 4q28.3 harbouring the PCDH10 gene. We demonstrate that PCDH10 transcription is down-regulated in 19/26 (73%) of medulloblastomas suggesting that other mechanisms also could be involved in gene repression. We found that DNA hypermethylation contributed to the deregulation of PCDH10 in 11/44 (25%) of medulloblastoma cell lines and primary tumours. Using a stable cell line (DAOY) re-expressing PCDH10, we observed that cell migration was impaired upon restoration of PCDH10 expression.

CONCLUSIONS:
Our findings suggest that genetic and epigenetic deregulation of PCDH10 occurs in a significant portion of medulloblastoma patients. Failure to express PCDH10 may result in loss of inhibition of cell migration, thereby contributing to medulloblastoma progression.

http://www.ncbi.nlm.nih.gov/pubmed/21597995

Silencing of PCDH10 is also a known cause Epileptic seizures and other cancers.

http://www.ihop-net.org/UniPub/iHOP/bng/101549.html

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