MYCN Amplification in RB1-Inactivated Retinoblastoma: Association With High-Risk Features

MYCN amplification occurs in a subset of retinoblastoma cases, both with and without RB1 inactivation. It has been suggested that retinoblastomas with MYCN amplification represent a distinct entity with more aggressive clinical behavior.

We examined the incidence of MYCN gain/amplification and RB1 inactivation in 192 unilateral retinoblastoma samples from children enucleated between 2011 and 2018 at the German reference center. MYCN copy number was assessed using quantitative PCR and confirmed by single nucleotide polymorphism microarray analysis. Clinical characteristics, RB1 mutation status, and histopathological features were compared between MYCN-amplified and nonamplified retinoblastomas.

MYCN gain/amplification was found in 10 of 139 retinoblastomas included in the final analysis (7.2%). All 10 tumors exhibited alterations in at least one RB1 allele (RB1^-/- or RB1^+/-). The RB1 mutation spectrum and overall genomic copy number changes were similar between MYCN-amplified and MYCN-nonamplified retinoblastomas. Age at diagnosis did not differ significantly between the two groups (p = 0.21); however, secondary glaucoma, massive choroidal, and scleral invasion occurred more often in MYCN-amplified retinoblastomas (p = 0.038, p = 0.03, and p = 0.04, respectively). No cases of extraocular retinoblastoma or distant metastasis were observed during a median follow-up of 50 months.

MYCN gain/amplification was identified in 7.2% of enucleated unilateral retinoblastomas, all of which showed RB1 inactivation. MYCN amplification was associated with more advanced disease and more aggressive clinical and histopathological features.