Diagnostic and prognostic information about retinoblastoma

Amy Gerrish, Edward Stone, Samuel Clokie, John R Ainsworth, Helen Jenkinson, Maureen McCalla, Carol Hitchcott, Isabel Colmenero, Stephanie Allen, Manoj Parulekar, Trevor Cole

Overview

To be able to get clear diagnostic and prognostic genetic information about retinoblastoma the tumour tissue needs to be examined. In the past this was not possible if the eye was not removed. By examining eye fluid we can generate this information in eyes that are not removed

Summary

Tthe management of retinoblastomahis is a novel approach that can revolutionise

Non-invasive diagnosis of retinoblastoma using cell-free DNA from aqueous humour.

Authors:
Professor Trevor Cole, MB ChB FRCP
Professor Trevor Cole, MB ChB FRCP
Birmingham Women's Hospital Healthcare NHS Trust
Professor
Cancer Genetics Endocrine Genetics
Birmingham, West Midlands | United Kingdom

Br J Ophthalmol 2019 Feb 11. Epub 2019 Feb 11.

West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.

Retinoblastoma is the most common eye malignancy in childhood caused by mutations in the gene. Both alleles of the gene must be mutated for tumour development. The initial mutation may be constitutional germline or somatic (originating in one retinal cell only). Distinguishing between these alternative mechanisms is crucial, with wider implications for management of the patient and family members. Bilateral retinoblastoma is nearly always due to a constitutional mutation; however, approximately 15% of unilateral cases also carry a germline mutation, and identifying these cases is important. This can be achieved by identifying both mutation types in tumour tissue and excluding their presence in blood. Modern eye-saving chemotherapy treatment (systemic, intra-arterial and intravitreal) has resulted in fewer enucleations. As a result, tumour tissue required to identify sporadic mutation(s) is not always available. Modern intravitreal chemotherapeutic techniques for retinoblastoma involve aspiration of aqueous humour (AH), providing a novel sample source for analysis. By analysing cell-free DNA present in the AH fluid of eyes affected with retinoblastoma, we have developed a screening test capable of detecting somatic mutations that is comparable to current tests on enucleated tumour tissue. The results obtained with fluid from enucleated eyes were concordant with tumour tissue in all 10 cases analysed. In addition, AH analysis from two patients undergoing intravitreal chemotherapy successfully identified somatic variants in both cases. Our findings suggest that AH fluid is a promising source of tumour-derived DNA in retinoblastoma for analysis.

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Source
http://bjo.bmj.com/lookup/doi/10.1136/bjophthalmol-2018-3130
Publisher Site
http://dx.doi.org/10.1136/bjophthalmol-2018-313005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709774PMC
February 2019
21 Reads
2.976 Impact Factor

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