# DETECTING INHERITED CANCER PREDISPOSITION VIA ONCOGENES

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1987 · $102,889

## Abstract

The purpose of this project is to determine the role of oncogenes in the
pathogenesis of malignancies occurring in neurofibromatosis (NF).
Dominantly inherited syndromes predisposing to neoplasia constitute an
important resource for study because individuals at high risk for
malignancies of specific types are identifiable years in advance.  The
sequence of mutations leading to malignancies may be identifiable by
comparison of malignant tissue, unaffected tissue from the same individual,
and tissue from unaffected individuals.  Of inherited syndromes
predisposing to neoplasia, neurofibromatosis is the most suitable for
analysis because it is dominant, common, and involves multiple tumors of
multiple types at accessible sites.  When NF patients have malignancies
resected, malignant and nontumor tissue will be obtained and DNA and RNA
purified.  In order to determine which oncogenes are hyperexpressed in
neurofibromatosis, poly A+ RNA will be purified from tumors and control
tissue and specific oncogene transcripts will be quantitated by RNA slot
blotting.  For any specific oncogene which is hyperexpressed in the tumor
compared to control tissue, size will be determined by Northern blotting.
For any specific oncogene which is hyperexpressed, gene number will be
determined by DNA slot blotting in order to determine whether the gene is
amplified.  To look for structural rearrangements, including large
deletions, insertions, or translocations, restriction mapping will be
performed.  If an abnormality in the restriction map is found, sequencing
will be performed.  To pursue our preliminary finding that sis and N-ras
may be hyperexpressed in NF neurofibrosarcomas, gene products will be
assayed by their activity (PDGF) or immunoreactivity (ras-like),
restriction fragment patterns of NF tumor tissue, NF non-tumor tissue, and
unaffected relatives will be compared to investigate the site of germline
and somatic mutations, and mutations in homologous genes will be
investigated by hybridization under conditions of reduced stringency.
Transforming activity of DNA from NF malignancies will be assayed in mouse
3T3 fibroblasts, human NF fibroblasts, and human non-NF fibroblasts.
Identification of oncogene abnormalities in neurofibromatosis may elucidate
the nature and sequence of mutational events, permit correlation of
clinical and cellular phenotypes with molecular genotypes, permit early
diagnosis in suspected cases, lead to prenatal diagnosis, and validate a
strategy applicable to other phakomatoses and dominantly inherited
predispositions to cancer.

## Key facts

- **NIH application ID:** 3176884
- **Project number:** 5R01CA038685-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** PETER T ROWLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $102,889
- **Award type:** 5
- **Project period:** 1986-09-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176884

## Citation

> US National Institutes of Health, RePORTER application 3176884, DETECTING INHERITED CANCER PREDISPOSITION VIA ONCOGENES (5R01CA038685-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176884. Licensed CC0.

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