Retinoblastoma genetics screening and clinical management

Abstract

Background India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. Methods Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. Results Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. Conclusions We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors

“…RB1 loss causes various alterations to cellular functions through transcriptional and epigenetic mechanisms [4], a greater understanding of which can provide novel treatment strategies. Although significant advances have been made to understand the genetics [5] and pathogenesis of retinoblastoma [6], it is still the most aggressive and fatal pediatric cancer in developing countries [7,8]. Rb is curable with global salvation strategies [9], and is universally fatal if left untreated.…”

Advancing precision medicines for ocular disorders: Diagnostic genomics to tailored therapies

“…In additional eight patients, MLPA identified deletion of one or more exons of PAX6 gene, demonstrating the necessity to screen for larger deletions in the gene in addition to sequencing of exons. Combinations of sequencing and MLPA are used routinely for the ocular pediatric tumor, Retinoblastoma (66).…”

Enhanced Epithelial-to-Mesenchymal Transition and Chemoresistance in Advanced Retinoblastoma Tumors Is Driven by miR-181a

“…Retinoblastoma (Rb) is the most common intraocular malignant tumor in children. Managing intraocular Rb tumors via efficient diagnoses, genetic screening, and clinical procedures [ 1 , 2 ] help to achieve excellent survival rates worldwide. However, metastatic retinoblastoma is still a major concern in many countries [ 3 , 4 , 5 ].…”