Abstract for presentation at 11th International Congress of Human Genetics

Molecular Progression from Retinoma to Retinoblastoma

  • Helen Dimaras, Ontario Cancer Institute/Princess Margaret Hospital, Canada
  • Dr William Halliday, The Hospital for Sick Children, Canada
  • Dr Vikas Khetan, The Hospital for Sick Children, Canada
  • Ms Nadia Prigoda, The Toronto Western Research Institute, Canada
  • Ms Marija Orlic, Ontario Cancer Institute/Princess Margaret Hospital, Canada
  • Dr Brenda Gallie, Ontario Cancer Institute/Princess Margaret Hospital, Canada

    • Purpose: Retinoma is a rare, clinically benign retinal tumor associated with constitutional mutation of the RB1 gene that, even more rarely, has been observed to progress to retinoblastoma. We examine the molecular basis of the transition from retinoma to retinoblastoma, and estimate the incidence of undiagnosed underlying retinoma in eyes primarily removed to treat retinoblastoma.
    Methods: Areas of retinoma and adjacent retinoblastoma and normal retina from human eyes were isolated from formalin-fixed, paraffin-embedded sections using laser capture microdissection. Genomic DNA and RNA were isolated and analyzed for RB1 mutation and quantitative RT-PCR for gene expression. Immunostaining was performed on serial sections of the same samples. A series of 100 eyes removed for retinoblastoma were examined for evidence of underlying retinoma.
    Results: We show that retinoma has mutation of both alleles of the RB1 gene, similar to retinoblastoma, and different from adjacent normal retina. Immunostaining confirms the lack of pRB expression in both retinoma and retinoblastoma. Quantitative RT-PCR revealed higher expression of candidate oncogenes in retinoblastoma than in retinoma and normal retina. Candidate tumor suppressor genes were expressed at higher levels in retinoma than retina, but decreased in retinoblastoma. The senescence gene p16 was highly expressed in both retinoma and retinoblastoma compared to normal retina, while immunostaining showed p16 cytoplasmic staining in retinoma, but not in retinoblastoma. Retinoblastoma, but not retinoma, stained strongly positive for Ki67, p53 and Bcl2. Retinoma, defined by these patterns of gene expression and frequent dysplastic differentiation to fleurettes, was documented in 15% (17/113) of eyes removed for treatment of retinoblastoma.
    Conclusion: Retinoma is a common intermediate step toward malignant retinoblastoma that molecularly shows little evidence of proliferation despite mutation of both RB1 alleles. Progression from retinoma to retinoblastoma involves several candidate oncogenes and tumor suppressor genes, including downregulation of p16 protein expression.

    Conference Organiser - ICMS Pty Ltd