• Driscoll, M. Catherine (PI)

Project: Research project

Project Details


Retinoblastoma (Rb) is an embryonal tumor of early childhood occuring at a
frequency of 1/23,000 live births. Approximately 40% of Rbs are due to a
germinal mutation expressed as a dominant trait. This mutation also
predisposes to the development of second nonocular malignancies notably
sarcomas. It is unclear if all Rb patients have the same risk of
developing second malignancies. Rb has served as a prototype for a model
of tumorigenesis proposed by Knudsen. This model requires two successive
event is germinal, while the second event may be chromosomal
loss/duplication, deletion, point mutation or mitotic recombination
resulting in functional loss of the normal allele. The recent observation
tumor, and rhabdomyosarcoma, however, suggests that a phenomenon called
genomic imprinting, may be involved in preferential inactivation of the
paternal genome in these tumors. Genomic imprinting is an epigenetic
process in which the expressivity/penetrance of a gene may be dependent
upon the parental origin. We propose to study the role of imprinting, if
any, in the development of second malignancies in hereditary Rb by, (1)
determining if there are tissue specific differences in methylation of
promotor in peripheral blood lymphocyte, retinoblastoma, and osteogenic
sarcoma DNA samples, (2) analyze constitutional and tumor (1o and 2o)
tissues for loss of heterozygosity, Rb gene deletions, Rb mRNA expression,
and parental origin. (3) analyze our pedigrees (where possible) for
parental origin of Rb gene in cases of nonocular malignancies.
Effective start/end date7/16/907/15/92


  • National Institutes of Health


  • Medicine(all)


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