# MOLECULAR GENETIC ANALYSIS OF HUMAN NEUROBLASTOMA

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1991 · $266,453

## Abstract

The long term focus of this laboratory is to identify and
characterize genes responsible for regulating growth and
differentiation in human neuroblastomas.  We have identified a
specific deletion of the short arm of chromosome 1 (at or distal
to 1p32).  This is the probable site of a putative neuroblastoma
(Nb) suppressor gene, the loss of which predisposes the cell to
malignant transformation.  We are taking a molecular approach to
identify and characterized the putative Nb gene.  Restriction
fragment length polymporphism (RFLP) and loss of heterozygosity
(LOH) will be used to localize the region that is consistently
deleted.  Then we will use pulsed-field gel electrophoresis (PFGE)
and yeast artificial chromosome (YAC) vector technology to clone
the region of interest.  Candidate gene(s) from this region that
are consistently deleted or rearranged in neuroblastomas will be
cloned and their patterns of expression characterized. Finally, we
will determine if the candidate gene(s) can induce differentiation
or suppress tumorigenicity by transfection into, neuroblastoma
cells in vitro, or injection of tansfected cells in nude mice.

We have demonstrated that the oncogene N-myc is amplified in about
a third of primary neuroblastomas.  We also have recent evidence
that 20-25% of tumors with a single copy of N-myc can overexpress
this gene at the mRNA and/or protein level.  We plan to analyze
human neuroblastomas for N-myc activation at the DNA, RNA or
protein level.  We will determine if some tumors without N-myc
amplification have activation of this gene by more precise analysis
of the amount and size of message, as well as the amount, size and
pattern of protein expression.

N-myc amplification is associated with advanced stages of disease,
rapid tumor progression and a poor prognosis in neuroblastoma
patients.  In addition, deletions of the short arm of chromosome
1 also appear to confer a poor prognosis, independent of N-myc
amplification.  We will determine the contribution of N-myc
activation and chromosome 1p deletions as prognostic markers in
this disease.

## Key facts

- **NIH application ID:** 3179192
- **Project number:** 5R01CA039771-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** GARRETT M BRODEUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $266,453
- **Award type:** 5
- **Project period:** 1985-05-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179192

## Citation

> US National Institutes of Health, RePORTER application 3179192, MOLECULAR GENETIC ANALYSIS OF HUMAN NEUROBLASTOMA (5R01CA039771-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179192. Licensed CC0.

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