This article is more than 5 years old. Information may no longer be current.
Retinoblastoma not linked solely to RB1 mutations, study finds
Click Here to Manage Email Alerts
Some cases of retinoblastoma may occur due to amplification of the MYCN oncogene rather than mutation of both alleles of the RB1 retinoblastoma suppressor gene, a study found.
In such nonhereditary cases, children may not be at heightened risk of retinoblastomas in the other eye, future cancers or further familial risk, the study authors wrote.
Researchers in the multicenter study analyzed 1,068 unilateral non-familial retinoblastoma tumors, comparing genomic copy number, RB1 gene expression and protein function, retinal gene expression, histological features and clinical data between tumors with no evidence of RB1 mutations and those with mutations in both alleles.
No RB1 mutations were observed in 29 tumors (2.7%), and 15 of those demonstrated high-level MYCN oncogene amplification.
Subjects in the study without RB1 mutation and with MYCN amplification tended to have larger and more aggressive tumors that included invasion into the optic nerve when compared with subjects of similar age with RB1 mutations, who tended to need active surveillance to discover the smaller tumors.
The authors predicted 18% of children diagnosed with non-familial unilateral retinoblastoma before the age of 6 months will have no RB1 mutations and MYCN amplification.
Perspective
Back to TopCarol L. Shields, MD
Retinoblastoma develops following mutation in the RB1 gene, a tumor suppressor gene. It is presumed that all eyes with retinoblastoma should show this mutation; however, the reality is that RB1 mutation is found in 94% of cases and the mutation remains undetectable in the remaining 6%. There has been an intense search for the “other” genetic mutation leading to retinoblastoma.
In this study by Rushlow et al, published online on March 13, 2013, new evidence was revealed that retinoblastoma can also be caused by MYCN oncogene activation. This indicates that retinoblastoma now has two potential mechanisms for the pathogenesis of this cancer.
In this study, evaluation of genetic mutations in 1,068 cases of unilateral sporadic retinoblastoma was performed. This was a collaborative effort from five clinical laboratories in Canada, Germany, France, New Zealand and the Netherlands. This team identified that 97.3% of cases had RB1 mutation on chromosome 13 and 2.7% (n = 29) showed no mutation. They searched for other mutational sites in those 29 patients without RB1 mutation and identified high level MYCN oncogene amplification in 15, a feature found in none of those with RB1 mutation (P < .0001). These authors noted that MYCN-related retinoblastoma was associated with younger age of tumor onset.
This study indicates that there are two pathways to the development of retinoblastoma. According to the authors, those with MYCN oncogene are at no increased risk for other cancers.
Click Here to Manage Email Alerts