title: Identification of the novel role of pRB in eye cancer.
abstract: Cancer of the eye, though relatively rare, can involve multiple areas. Retinoblastoma is the most common primary intraocular cancer in children, with 3-7 cases per million people per year worldwide. Uveal melanoma is the most common primary intraocular cancer in adults, predominately in whites, with annual incidence of six per million people in the United States and Europe. Despite the rarity of retinoblastoma, Knudson's two-hit hypothesis to explain its genesis was substantiated by elegant genetic studies and is viewed as a turning point in cancer research. pRB plays an important role in cell cycle and apoptosis, performing its function through interaction with transcription factors, p53, and MDM2. Unfortunately, advances in eye cancer treatment have not paralleled those in treatment of other sites of cancer. In spite of higher accuracy in early diagnosis, eye-cancer-specific mortalities have remained unchanged for decades, while overall cancer mortality rates have dramatically declined. An extensive literature search revealed that, except for retinoblastoma, few investigations had been done on the pRB pathway in eye cancers even though altered pRB expression has been associated with a number of cancers. Early detection of eye cancer is critical for the prognosis of both vision and survival. Mutation analysis should become an integral part of future management of patients with eye cancer. Characterization of the mutational pattern of RB1 is crucial in identifying predisposition for cancer of many sites including the eye. Furthermore, cost-effective and efficient genetic mutation screen testing methods, which can be used to categorize mutant RB1 carriers, are needed. Illumination of genetic insights can guide clinicians to develop a rational strategy for cancer treatment and help predict prognosis in cancer patients.
authors.affiliation: Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. hong.lai@jhu.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Lai
authors.forename: Fangchao
authors.initials: F
authors.lastname: Ma
authors.forename: Shenghan
authors.initials: S
authors.lastname: Lai
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D005134:Eye Neoplasms / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012175:Retinoblastoma / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014604:Uveal Neoplasms / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2