Gene expression profiling identifies different sub-types of retinoblastoma

Background: Mutation of the RB1 gene is necessary but not sufficient for the development of retinoblastoma. The nature of events occurring subsequent to RB1 mutation is unclear, as is the retinal cell-of-origin of this tumour. Methods: Gene expression profiling of 21 retinoblastomas was carried out to identify genetic events that contribute to tumorigenesis and to obtain information about tumour histogenesis. Results: Expression analysis showed a clear separation of retinoblastomas into two groups. Group 1 retinoblastomas express genes associated with a range of different retinal cell types, suggesting derivation from a retinal progenitor cell type. Recurrent chromosomal alterations typical of retinoblastoma, for example, chromosome 1q and 6p gain and 16q loss were also a feature of this group, and clinically they were characterised by an invasive pattern of tumour growth. In contrast, group 2 retinoblastomas were found to retain many characteristics of cone photoreceptor cells and appear to exploit the high metabolic capacity of this cell type in order to promote tumour proliferation. Conclusion: Retinoblastoma is a heterogeneous tumour with variable biology and clinical characteristics. Kapatai, G et al. Br J Cancer (2013) 109, 512-525 doi: 10.1038/bjc.2013.283 Frozen tissue from 21 retinoblastomas, enucleated without prior treatment, was used for microarray analyses. A comparison was made with data from normal human fetal (GSM460264) and adult (GSM607947, GSM607948) retina. The complete dataset with total 24 data columns (including three re-analyzed data from Series GSE18487, GSE24673) is linked below as a supplementary file.