Epigenetics in Retinoblastoma / Aus der Reihe: e-fellows.net stipendiaten-wissen Bd.Band 619 (PDF)

Essay from the year 2012 in the subject Medicine - Ophthalmology, grade: 1,3, University of Heidelberg, language: English, abstract: Today's DNA sequencing technologies are becoming more and more impressive. That it is not only important to focus on mutations in the sequence of DNA, however, but also on differences that occur on the level above the genes, the epigenetic modifications of the DNA, has been found out by the researchers of Michael Dyer's group.
The quickly developing childhood cancer retinoblastoma is directly related to the inactivation of the tumor suppressor gene RB1. With RB1 having different roles relevant for understanding this cancer, the process leading to advancing retinoblastoma after its inactivation is not yet understood.
After analysis of the genome and the epigenome of different retinoblastomas, the genome was detected as relatively stable. A newly proposed part of the chain of events leading to the outbreak of this severe cancer is as follows.
Biallelic loss of RB1 leads to the deregulation of epigenetic mechanisms and thereby also of cancer pathways. This is followed by cells acquiring the characteristics of cancer cells. With the experiments conducted by Dyer et al., the proto-oncogene SYK (spleen tyrosine kinase) was found to be upregulated in retinoblastoma and also necessary for the survival of the tumor cells. With SYK inhibited, increasing apoptosis of the cancer cells could be observed. The conclusion seems likely that SYK promises to be a new target for treating retinoblastoma patients and a broader approach in research, including not only genomic data, but also epigenetic analyses, is necessary for better understanding of cancer in the future.