Molecular changes in retinoblastoma beyond RB1: Findings from next-generation sequencing Journal Article
| Authors: | Francis, J. H.; Richards, A. L.; Mandelker, D. L.; Berger, M. F.; Walsh, M. F.; Dunkel, I. J.; Donoghue, M. T. A.; Abramson, D. H. |
| Article Title: | Molecular changes in retinoblastoma beyond RB1: Findings from next-generation sequencing |
| Abstract: | This investigation uses hybridization capture-based next-generation sequencing to deepen our understanding of genetics that underlie retinoblastoma. Eighty-three enucleated retinoblas-toma specimens were evaluated using a MSK-IMPACT clinical next-generation sequencing panel to evaluate both somatic and germline alterations. Somatic copy number variations (CNVs) were also identified. Genetic profiles were correlated to clinicopathologic characteristics. RB1 inactivation was found in 79 (97.5%) patients. All specimens had additional molecular alterations. The most common non-RB1 gene alteration was BCOR in 19 (22.9%). Five (11.0%) had pathogenic germline mutations in other non-RB1 cancer predisposition genes. Significant clinicopathologic correlations included: vitreous seeds associated with 1q gains and 16q loss of heterozygosity (BH-corrected p-value = 0.008, 0.004; OR = 12.6, 26.7, respectively). BCOR mutations were associated with poor prognosis, specifically metastases-free survival (MFS) (nominal p-value 0.03). Furthermore, retinoblastoma patients can have non-RB1 germline mutations in other cancer-associated genes. No two specimens had the identical genetic profile, emphasizing the individuality of tumors with the same clinical diagnosis. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| Keywords: | retinoblastoma; next-generation sequencing; bcor; vitreous seeds; copy number variations |
| Journal Title: | Cancers |
| Volume: | 13 |
| Issue: | 1 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2021-01-01 |
| Start Page: | 149 |
| Language: | English |
| DOI: | 10.3390/cancers13010149 |
| PROVIDER: | scopus |
| PMCID: | PMC7796332 |
| PUBMED: | 33466343 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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