Next-generation sequencing-based method shows increased mutation detection sensitivity in an Indian retinoblastoma cohort.

Autor:	Singh J; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Mishra A; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Pandian AJ; Sankara Nethralaya ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India., Mallipatna AC; Department of Pediatric Ophthalmology and Strabismology, Narayana Nethralaya, Bangalore, India., Khetan V; Department of Vitreo Retina, Sankara Nethralaya, Chennai, India., Sripriya S; Sankara Nethralaya ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India., Kapoor S; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Agarwal S; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Sankaran S; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Katragadda S; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Veeramachaneni V; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Hariharan R; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India; Department of Computer Science and Automation, Indian Institute of Science, Bangalore, India., Subramanian K; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India., Mannan AU; Strand Center for Genomics and Personalized Medicine, Strand Life Sciences, Bangalore, India.
Jazyk:	angličtina
Zdroj:	Molecular vision [Mol Vis] 2016 Aug 16; Vol. 22, pp. 1036-47. Date of Electronic Publication: 2016 Aug 16 (Print Publication: 2016).
Abstrakt:	Purpose: Retinoblastoma (Rb) is the most common primary intraocular cancer of childhood and one of the major causes of blindness in children. India has the highest number of patients with Rb in the world. Mutations in the RB1 gene are the primary cause of Rb, and heterogeneous mutations are distributed throughout the entire length of the gene. Therefore, genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. Methods: In this study, we screened the RB1 gene in the DNA isolated from blood or saliva samples of 50 unrelated patients with Rb using the TruSight Cancer panel. Next-generation sequencing (NGS) was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. Results: We were able to detect germline pathogenic mutations in 66% (33/50) of the cases, 12 of which were novel. We were able to detect all types of mutations, including missense, nonsense, splice site, indel, and structural variants. When we considered bilateral Rb cases only, the mutation detection rate increased to 100% (22/22). In unilateral Rb cases, the mutation detection rate was 30% (6/20). Conclusions: Our study suggests that NGS-based approaches increase the sensitivity of mutation detection in the RB1 gene, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode.
Databáze:	MEDLINE
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