An overview of transcript alterations detected during retinoblastoma genetic screening.

Identification of pathogenic variants aids in the clinical management of families with retinoblastoma. We routinely screen DNA for variants, but transcript analysis can also be used for variant screening, and to help decide variant pathogenicity. DNA was screened by conformation analysis followed by Sanger sequencing.

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

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.

Whole-Genome Sequencing of Retinoblastoma Reveals the Diversity of Rearrangements Disrupting and Uncovers a Treatment-Related Mutational Signature.

The development of retinoblastoma is thought to require pathological genetic changes in both alleles of the gene. However, cases exist where mutations are undetectable, suggesting alternative pathways to malignancy. We used whole-genome sequencing (WGS) and transcriptomics to investigate the landscape of sporadic retinoblastomas derived from twenty patients, sought and other driver mutations and investigated mutational signatures.

Prognostic Information for Known Genetic Carriers of RB1 Pathogenic Variants (Germline and Mosaic).

Purpose: To compare the number of tumors per eye for mosaic carriers of RB1 pathogenic variants with full germline variants and the conversion from unilateral to bilateral disease.

Design: Retrospective cohort study comparing patients with retinoblastoma and different genetic subtypes: high penetrance (HP), low penetrance (LP), and mosaicism.

Participants: Data were analyzed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London, United Kingdom.

Number, frequency and time interval of examinations under anesthesia in bilateral retinoblastoma.

Purpose: Current practice in retinoblastoma (Rb) has transformed this malignancy into a curable disease. More attention should therefore be given to quality of life considerations, including measures related to examinations under anesthesia (EUAs). We aimed to investigate EUA measures in bilateral Rb patients and compare the findings to EUAs in unilateral Rb.

Examinations under anaesthesia as a measure of disease burden in unilateral retinoblastoma: the London experience.

Background: Early diagnosis strategies and advances in retinoblastoma (Rb) management have resulted in nearly 100% survival. More attention should, therefore, be given to quality of life considerations. We aimed to quantify the number of examinations under anaesthesia (EUAs) in a cohort of patients with Rb, as a measure of disease burden.

Strabismus in retinoblastoma survivors with long-term follow-up.

Purpose: To report the long-term strabismus rate in salvaged retinoblastoma (Rb) patients and investigate possible risk factors leading to strabismus.

Methods: The medical records of patients with Rb presenting at a single institution over a 9-year period were reviewed retrospectively with regard to ocular alignment outcomes after long-term follow-up.

Results: A total of 64 eyes of 42 patients (22 bilateral cases [52%]) were included, presenting with International Intraocular Retinoblastoma Classification (IIRC) in the worse eye as follows: group A (n = 1), B (n = 16), C (n = 12), D (n = 11), no Rb (n = 2).

Detection and reporting of RB1 promoter hypermethylation in diagnostic screening.

Background: RB1 gene screening aids clinical management and genetic counselling in retinoblastoma families. Here we present epigenetic changes identified during routine molecular RB1 screening of tumor and blood samples. Complications in interpreting RB1 methylation are discussed.

The management of retinoblastoma.

Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of 1:15,000-1:20,000 live births. Despite its rarity, Rb has served as a cornerstone in the field of oncology in many of the aspects that comprise cancer management, including classification schemes, treatment modalities, genetic testing and screening. Until just over half a century ago, the major treatment for Rb was eye removal, and prognosis was poor with outcome fatal for most children.

THE RECOGNITION OF CAVITARY RETINOBLASTOMA TUMORS: Implications for Management and Genetic Analysis.

Purpose: To assess the role of consolidating adjuvant therapy for cavitary retinoblastoma and to understand if there is any phenotype-genotype correlation.

Methods: Patients with retinoblastomas having ophthalmoscopically visible cavities between 2004 and 2014 in whom 4 to 6 cycles of systemic chemotherapy were given.

Results: Eighteen eyes of 17 patients displayed cavitary retinoblastomas.

Primary intravenous chemotherapy for group D retinoblastoma: a 13-year retrospective analysis.

Background: Eye salvage rate for group D retinoblastoma using intravenous chemotherapy (IVC) as a primary modality is <50%. To report on 13 years' experience with the use of primary IVC for group D retinoblastoma.

Methods: A retrospective analysis of 64 group D eyes (52 patients) treated with primary IVC, from 2002 to 2014.

Extensive Variation in the Mutation Rate Between and Within Human Genes Associated with Mendelian Disease.

We have investigated whether the mutation rate varies between genes and sites using de novo mutations (DNMs) from three genes associated with Mendelian diseases (RB1, NF1, and MECP2). We show that the relative frequency of mutations at CpG dinucleotides relative to non-CpG sites varies between genes and relative to the genomic average. In particular we show that the rate of transition mutation at CpG sites relative to the rate of non-CpG transversion is substantially higher in our disease genes than amongst DNMs in general; the rate of CpG transition can be several hundred-fold greater than the rate of non-CpG transversion.

Spectrum of RB1 mutations identified in 403 retinoblastoma patients.

Background: Retinoblastoma (RB) is a malignant, childhood tumour of the developing retina that occurs with an estimated frequency of 1 in 20 000. Identification of oncogenic mutations in the RB1 gene aids in the clinical management of families with a heritable predisposition to RB. Here we present the spectrum of genetic and epigenetic changes identified in 194 tumours and 209 blood samples, from 403 unrelated RB patients.

A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus.

Altered methylation patterns have been found to play a role in developmental disorders, cancer and aging. Increasingly, changes in DNA methylation are used as molecular markers of disease. Therefore, there is a need for reliable and easy to use techniques to detect and measure DNA methylation in research and routine diagnostics.

Genomic alterations in blastic natural killer/extranodal natural killer-like T cell lymphoma with cutaneous involvement.

Natural killer and natural killer-like T cell lymphomas represent a rare type of non-Hodgkin's lymphoma originally described to involve the upper aerodigestive tract. This malignancy has been increasingly observed in other extranodal sites, particularly in the skin. Patients with cutaneous natural killer cell lymphoma generally have a poor prognosis; however, the etiology and the underlying molecular pathogenesis remain unclear.

The chemosensitivity profile of retinoblastoma.

Retinoblastoma is a rare malignant tumour of the developing retina with an incidence of 1 in 20,000 live births in all human races. Chemotherapy is used in retinoblastoma as adjuvant therapy to prevent the growth of metastases and to treat metastatic disease once this has become clinically apparent. Current regimens are based on empirical drug combinations, and few clinical trials have been conducted because of the rarity of this tumour.

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology, progression, and patient outcome.

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors.