# MOLECULAR GENETIC ANALYSIS OF HUMAN NEUROBLASTOMA

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 1993 · $258,750

## Abstract

Neuroblastomas are characterized genetically by deletion of the distal
short arm of chromosome 1 (1p36), and amplification of the N-myc proto-
oncogene.  Indeed, these two features characterize a very aggressive
subset of neuroblastomas.  We have localized the region of consistent
deletion in these tumors to 1p36.1.  There is recent evidence that
deletion or rearrangement of this locus may be responsible for genetic
predisposition to develop neuroblastoma.  We hypothesize that a
neuroblastoma suppressor gene (NB1) is located in this region.  Deletion
or mutation of this gene constitutionally may predispose to development
of neuroblastoma, and homozygous deletion or inactivation in a single
neuroblast may be an important step in the development of this disease.
We plan to clone the region of consistent deletion (estimated to be <2
Mb) in YACS and identify expressed sequences in the region.  Then we will
determine which gene is consistently deleted or rearranged in
neuroblastomas in order to identify and characterize the NB1 suppressor
gene.  In addition, we will determine the prevalence of mutations of this
gene in neuroblastomas, as well as in constitutional DNA of familial
cases.

N-myc amplification is highly associated with advanced stages of disease
and rapid tumor progression.  N-myc does not appear to be activated
frequently by other mechanisms, and no other oncogenes have been shown
to be amplified or otherwise activated in these tumors.  Recently we have
cloned and mapped an entire N-myc amplicon from a neuroblastoma cell
line.  The amplicon was 1.2 Mb and had a circular, head-to-tail
organization.  We propose to develop a high-resolution cosmid map of the
core domain flanking the N-myc gene that is consistently amplified in
neuroblastomas to identify any other expressed sequences that might
contribute to the malignant phenotype associated with N-myc amplification
(rapid growth, invasion, metastasis, resistance to treatment).  Also, we
will identify and characterize sites of recombination that have led to
or resulted from the amplification process.  Together, these findings
should provide substantial insights into the mechanisms that result in
this clinically important rearrangement in neuroblastomas, and possibly
other tumors with oncogene amplification.

Finally, some tumor samples cannot have N-myc copy number determined
because they are too small, degraded or fixed.  We are developing a PCR-
based technique to identify N-myc amplification in these cases.  In
addition, we are developing a fluorescence in-situ hybridization (FISH)
approach to analyze mixed samples of normal and tumor cells.  Together
these techniques will be more rapid and efficient.  They will be extended
to all samples studied, and they should allow us to address issues of
tumor heterogeneity and progression within and between primary and
metastatic lesions.

## Key facts

- **NIH application ID:** 3179186
- **Project number:** 2R01CA039771-09
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **SAM.gov UEI:** G7MQPLSUX1L4
- **Principal Investigator:** GARRETT M BRODEUR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $258,750
- **Award type:** 2
- **Project period:** 1985-05-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179186

## Citation

> US National Institutes of Health, RePORTER application 3179186, MOLECULAR GENETIC ANALYSIS OF HUMAN NEUROBLASTOMA (2R01CA039771-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179186. Licensed CC0.

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