Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Partial inactivation of the RB product in a family with incomplete penetrance of familial retinoblastoma and benign retinal tumors.

Publication ,  Journal Article
Kratzke, RA; Otterson, GA; Hogg, A; Coxon, AB; Geradts, J; Cowell, JK; Kaye, FJ
Published in: Oncogene
May 1994

While familial retinoblastoma has served as the paradigm for the two-hit theory of tumorigenesis and for the concept of the tumor suppressor gene, the etiology of incomplete penetrance of familial retinoblastoma is poorly understood. To address the molecular basis for this phenotype we have studied the functional properties of a mutant Rb gene identified in a kindred with incomplete penetrance of familial retinoblastoma and evidence for regressed retinal lesions (retinomas). In contrast to all previously isolated RB mutant proteins, we demonstrated that the mutant product from this kindred retained the wildtype properties of nuclear localization, the ability to undergo hyperphosphorylation in vivo, and the capacity to suppress growth of RB(-) cells. Protein binding ('pocket') activity, however, was defective defining a new class of RB mutant with partial inactivation. The presence of this unique RB mutant in the germline of obligate carriers with incomplete penetrance and regressed retinal lesions suggests a molecular basis for this phenotype and supports the hypothesis that a minimum 'RB threshold' level of protein binding activity is required to suppress tumorigenesis.

Duke Scholars

Published In

Oncogene

ISSN

0950-9232

Publication Date

May 1994

Volume

9

Issue

5

Start / End Page

1321 / 1326

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Retinoblastoma Protein
  • Retinoblastoma
  • Point Mutation
  • Phosphorylation
  • Phenotype
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Humans
  • Genes, Retinoblastoma
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kratzke, R. A., Otterson, G. A., Hogg, A., Coxon, A. B., Geradts, J., Cowell, J. K., & Kaye, F. J. (1994). Partial inactivation of the RB product in a family with incomplete penetrance of familial retinoblastoma and benign retinal tumors. Oncogene, 9(5), 1321–1326.
Kratzke, R. A., G. A. Otterson, A. Hogg, A. B. Coxon, J. Geradts, J. K. Cowell, and F. J. Kaye. “Partial inactivation of the RB product in a family with incomplete penetrance of familial retinoblastoma and benign retinal tumors.Oncogene 9, no. 5 (May 1994): 1321–26.
Kratzke RA, Otterson GA, Hogg A, Coxon AB, Geradts J, Cowell JK, et al. Partial inactivation of the RB product in a family with incomplete penetrance of familial retinoblastoma and benign retinal tumors. Oncogene. 1994 May;9(5):1321–6.
Kratzke RA, Otterson GA, Hogg A, Coxon AB, Geradts J, Cowell JK, Kaye FJ. Partial inactivation of the RB product in a family with incomplete penetrance of familial retinoblastoma and benign retinal tumors. Oncogene. 1994 May;9(5):1321–1326.

Published In

Oncogene

ISSN

0950-9232

Publication Date

May 1994

Volume

9

Issue

5

Start / End Page

1321 / 1326

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Retinoblastoma Protein
  • Retinoblastoma
  • Point Mutation
  • Phosphorylation
  • Phenotype
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Humans
  • Genes, Retinoblastoma