Gene expression profiling identifies different sub-types of retinoblastoma

Kapatai, Georgia; Ma, Brundler; Jenkinson, Helen; Kearns, Pamela; Parulekar, Manoj; Peet, Andrew C.; Cm, McConville

doi:10.1038/bjc.2013.283

Cited by 78 publications

(88 citation statements)

References 56 publications

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“…52 Gene expression profiles were initially proposed to reveal only a single relatively homogeneous class of retinoblastoma 55 and were subsequently proposed to segregate RB1 −/− retinoblastomas into two subtypes. 56 However, analyses of a larger cohort recently revealed a spectrum of phenotypes reflecting progression from a state with high photoreceptor differentiation and few cytogenetic changes to a state with lower differentiation, increased mRNA and ribosome biogenesis and mitosis gene expression signatures, and increased cytogenetic aberrations. 54 Thus, RB1 −/− retinoblastomas appear to progress from self-limiting retinomas to differentiated retinoblastoma to less differentiated malignancies.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Retinoblastoma

Dimaras

Corson

Cobrinik

et al. 2015

Nat Rev Dis Primers

468

390

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Retinoblastoma is a rare cancer of the infant retina, which forms when both RB1 alleles mutate in a susceptible retinal cell, likely a cone photoreceptor precursor. Loss of the tumour suppressor functions of the retinoblastoma protein, pRB, leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in virtually all tissues, cone precursors have biochemical and molecular features that may sensitize to RB1 loss to enable tumourigenesis. Retinoblastoma is diagnosed in ~8,000 children each year worldwide. Patient survival is >95% in high-income countries, but <30% globally. However, outcomes are improving through increasing awareness for earlier diagnosis, new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted since survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma as well as second cancers in patients with germline RB1 mutations.

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Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Retinoblastoma

Dimaras

Corson

Cobrinik

et al. 2015

Nat Rev Dis Primers

468

390

View full text Add to dashboard Cite

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“…85-88 Gene expression profiling (GEP) of mRNA and comparative genomic hybridization (CGH) of DNA were utilized recently to evaluate 21 retinoblastomas. 89 Results of this initial study showed different patterns of retinal gene expression that when analyzed by unsupervised hierarchical clustering, followed by principle component analysis to categorize the retinoblastomas into three groups. 89 Group 1 retinoblastomas expressed genes found in early retinal development, thus suggesting a RPC origin.…”

Section: Molecular Biologymentioning

confidence: 99%

Retinoblastoma. Fifty Years of Progress. The LXXI Edward Jackson Memorial Lecture

Grossniklaus¹

2014

American Journal of Ophthalmology

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Purpose To review the progress made in understanding the genetic basis, molecular pathology, and treatment of retinoblastoma since the previous Jackson lecture on the topic was published 50 years ago. Design Perspective based on personal experience and the literature. Methods The literature regarding retinoblastoma was reviewed since 1963. Advances in understanding the biology and treatment of retinoblastoma provided context through the author’s clinical, pathological and research experiences. Results Retinoblastoma was first identified in the 1500s and defined as a unique clinicopathologic entity in 1809. Until the mid-1900s, knowledge advanced sporadically, with technological developments of ophthalmoscopy and light microscopy, and with the introduction of surgical enucleation, chemotherapy and radiation therapy. During the last 50 years, research and treatment have progressed at an unprecedented rate due to innovations in molecular biology and the development of targeted therapies. During this time period, the retinoblastoma gene was discovered; techniques for genetic testing for retinoblastoma were developed; and plaque brachytherapy, chemoreduction, intraarterial chemotherapy, and intraocular injections of chemotherapeutic agents were successfully introduced. Conclusions Nearly all patients with retinoblastoma in developed countries can now be cured of their primary cancer- a remarkable achievement for a childhood cancer that once was uniformly fatal. Much of this success is owed to deciphering the role of the Rb gene, and the benefits of targeted therapies, such as chemoreduction with consolidation as well as intra-arterial and intravitreal chemotherapies. Going forward, the main challenge will be ensuring that access to care is available for all children, particularly those in developing countries.

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“…Analysis of gene expression profiles in Rb patients has revealed that there are two types of Rb, each with a specific cell of origin. Unlike the second type, the first type exhibits an invasive growth pattern [89]. Spread of tumor cells from the primary site to distant organs requires the acquisition of specific features such as invasion, intravasation, survival in the circulation, extravasation and, finally, colonization within the target organ.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%