The RB1 Story: Characterization and Cloning of the First Tumor Suppressor Gene

Jesse L Berry; Ashley Polski; Webster K Cavenee; Thaddeus P Dryja; A Linn Murphree; Brenda L Gallie

doi:10.3390/genes10110879

The RB1 Story: Characterization and Cloning of the First Tumor Suppressor Gene

Genes (Basel). 2019 Nov 1;10(11):879. doi: 10.3390/genes10110879.

Authors

Jesse L Berry^{1

2}, Ashley Polski^{3

4}, Webster K Cavenee^{5

6

7}, Thaddeus P Dryja⁸, A Linn Murphree^{9

10}, Brenda L Gallie^{11

12

13}

Affiliations

¹ USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA. jesse.berry@med.usc.edu.
² The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA. jesse.berry@med.usc.edu.
³ USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA. ashley.polski@usc.edu.
⁴ The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA. ashley.polski@usc.edu.
⁵ Ludwig Institute for Cancer Research, University of California, San Diego, CA 92093, USA. wcavenee@ucsd.edu.
⁶ Department of Medicine, UCSD School of Medicine, San Diego, CA 92093, USA. wcavenee@ucsd.edu.
⁷ Moores Cancer Center, UCSD School of Medicine, San Diego, CA 92093, USA. wcavenee@ucsd.edu.
⁸ Cogan Eye Pathology Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. thaddeus_dryja@meei.harvard.edu.
⁹ USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA. alm4@mac.com.
¹⁰ The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA. alm4@mac.com.
¹¹ Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada. brenda@gallie.ca.
¹² Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON M5T 3A9, Canada. brenda@gallie.ca.
¹³ Departments of Molecular Genetics and Medical Biophysics, University of Toronto, Toronto, ON M5T 3A9, Canada. brenda@gallie.ca.

Abstract

The RB1 gene is the first described human tumor suppressor gene and plays an integral role in the development of retinoblastoma, a pediatric malignancy of the eye. Since its discovery, the stepwise characterization and cloning of RB1 have laid the foundation for numerous advances in the understanding of tumor suppressor genes, retinoblastoma tumorigenesis, and inheritance. Knowledge of RB1 led to a paradigm shift in the field of cancer genetics, including widespread acceptance of the concept of tumor suppressor genes, and has provided crucial diagnostic and prognostic information through genetic testing for patients affected by retinoblastoma. This article reviews the long history of RB1 gene research, characterization, and cloning, and also discusses recent advances in retinoblastoma genetics that have grown out of this foundational work.

Keywords: cancer genetics; gene cloning; genetic testing; retinoblastoma; tumor suppressor gene.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Cloning, Molecular
Genes, Tumor Suppressor*
Humans
Retinoblastoma / diagnosis
Retinoblastoma / genetics*
Retinoblastoma Binding Proteins / genetics*
Retinoblastoma Binding Proteins / metabolism
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / metabolism

Substances

Biomarkers, Tumor
RB1 protein, human
Retinoblastoma Binding Proteins
Ubiquitin-Protein Ligases

Grants and funding

K08 CA232344/CA/NCI NIH HHS/United States