MYCN amplification levels in primary retinoblastoma tumors analyzed by Multiple Ligation-dependent Probe Amplification

• Published in: Ophthalmic genetics Vol. 42; no. 5; pp. 604 - 611
• Main Authors: Price, Elizabeth A, Patel, Roopal, Scheimberg, Irene, Kotiloglu Karaa, Esin, Sagoo, Mandeep S, Reddy, M Ashwin, Onadim, Zerrin
• Format: Journal Article
• Language: English
• Published: England 01.10.2021
• Subjects: Child; Child, Preschool; Exons; Female; Gene Amplification - genetics; Genetic Testing; Humans; Infant; Male; N-Myc Proto-Oncogene Protein - genetics; Nucleic Acid Amplification Techniques - methods; Retinal Neoplasms - genetics; Retinal Neoplasms - pathology; Retinoblastoma - genetics; Retinoblastoma - pathology; Retinoblastoma Binding Proteins - genetics; Ubiquitin-Protein Ligases - genetics; RB1; genetic; sporadic; somatic; MYCN; Retinoblastoma
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2021.1923038

Retinoblastoma (Rb) is a childhood tumor of the developing retina where predisposition is caused by pathogenic variants. amplification ( ) has been implicated in around 2% of sporadic unilateral Rb tumors with no detectable variants. We audited data from tumors collected between 1993 and 2019 to determine if this is the case for patients treated at Barts Health NHS Trust, and how often it occurred alongside variants. Screening for was carried out by Multiple Ligation Probe Analysis of tumor and blood samples collected for genetic screening. The cohort consisted of 149 tumors, of which 114 had matched blood samples. 10/149 (6.7%) tumors were positive for in a population containing a disproportionate number of cases negative for pathogenic variants. Of 65 unbiased tumors collected from 2014 to 2019, 2 (3.1%) had . All samples were from sporadic, unilateral patients and 3/10 (30%) had pathogenic variants. was not detected in any blood sample. No tumor had 6p gain which is usually a common alteration in Rbs. occurs in a small fraction of Rbs and can occur in the presence of pathogenic variants. However, where it occurs alongside alterations, the age of onset appears to be later. has yet to be seen as a heritable change. In sporadic cases with early diagnosis, Rbs with no pathogenic variant identified should be tested for . Conversely, tumors with should still be screened for pathogenic variants.