The der(X) region harboring the RB1 gene was inactivated in a subset of somatic cells, including the retinal cells, in the patient subject which acted as the first hit in the development of her retinoblastoma.
This study might be an important report on emphazing the mutational status of other genes in patients without RB1 gene mutations and having high risk for developing Rb.
This is especially important for survivors of heritable cancers such as retinoblastoma (childhood eye cancer), where survivors who carry a germline mutation in the RB1 gene are at increased risk of second cancers in adulthood, and of passing on the disease risk to future offspring.
In human primary retinoblastoma, high expression of UHRF1 and XRCC4 could be detected, and elevated XRCC4 expression correlated with reduced apoptosis markers, implying that UHRF1-mediated XRCC4 upregulation under pathophysiological conditions triggered by RB1 gene inactivation may confer protection against endogenous DNA damages that arise during retinoblastoma development.
Although RB1 gene mutation underlies the development of retinoblastoma and many other systemic cancers, RB1 gene mutation in a brain tumor is mainly limited to infiltrating gliomas.
Here, we show that SUV39H1-mediated H3K9 trimethylation facilitates retinoblastoma ( RB) 1 promoter CpG island methylation by interacting with DNA methyltransferase 3A and decreasing RB mRNA and protein in melanoma cells.
The C allele together with a germ-line RB1 gene mutation may speed retinoblastoma onset which suggests that mir-34b/c rs4938723T > C may represent a candidate biomarker for hereditary RB.
It has been demonstrated by previous studies that retinoblastoma is initiated primarily by the inactivation of the retinoblastomaRb1 gene in retinal cells.
Silencing by methylation of the RB1 promoter has been observed in retinoblastoma tumors as a second mutation (M2) and is classified as somatic epimutation.