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Spectrum of RB1 mutations identified in 403 retinoblastoma patients
  1. Elizabeth A Price1,
  2. Kelly Price1,
  3. Kelly Kolkiewicz1,
  4. Simon Hack1,2,
  5. M Ashwin Reddy3,
  6. John L Hungerford3,4,
  7. Judith E Kingston3,
  8. Zerrin Onadim1
  1. 1Retinoblastoma Genetic Screening Unit, Barts Health NHS Trust, London, UK
  2. 2University College, London, UK
  3. 3Retinoblastoma Service, Barts Health NHS Trust, London, UK
  4. 4Moorfields Eye Hospital, London, UK
  1. Correspondence to Dr Zerrin Onadim, Retinoblastoma Genetic Screening Unit, Molecular Pathology Suite, 3rd Floor, Pathology & Pharmacy Building, 80 Newark Street, London E1 2ES, UK; zerrin.onadim{at}


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.

Methods Mutation screening was carried out across all 27 RB1 exons and their associated splice sites. Small coding sequence changes were detected using fluorescent conformation analysis followed by sequencing. Large exonic deletions were detected by quantitative fluorescent PCR. Methylation specific PCR of the RB1 promoter was performed to detect epigenetic alterations. Polymorphism analysis was used to determine loss of heterozygosity in tumour samples.

Results 95% of the expected mutations were identified in the tumour samples, with 16 samples exhibiting only one mutation, while two samples had no detectable RB1 mutation. 96% of bilateral/familial RB blood samples and 9.5% of unilateral sporadic blood samples, yielded mutations. 111 were novel mutations.

Conclusions The full range of screening techniques is required to achieve a high screening sensitivity in RB patients.

  • Genetic Screening/Counselling

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