# ISOLATION OF AMPLIFIED GENES FROM HUMAN TUMORS

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 1989 · $177,541

## Abstract

Isolation of genes that are amplified in tumor cells provides a
promising approach to identification of previously unknown genes
involved in carcinogenesis and tumor progression.  The technique
of in-gel DNA renaturation was developed for detection and
cloning of amplified genes of unknown nature.  A new method
which permits detection of DNA sequences amplified as little as
7- to 8-fold has been developed on the basis of this procedure.
Two new cases of gene amplification in tumor cell lines have
already been found which this new technique.  In the first case
erbA1 was amplified in Calu-3 lung adenocarcinoma, and in the
second case amplification of the c-myc gene was associated with
selection of PC-3 prostatic carcinoma cells for growth in nude
mice.  To understand the significance of in vivo amplification of
the c-myc gene, PC-3 cells will be analyzed to determine whether
c-myc is rearranged or non-uniformly amplified in unselected
cells, and whether increased c-myc amplification provides PC-3
cells with a selective advantage for in vivo growth.  To find
previously unknown amplified genes associated with
carcinogenesis and tumor progression, a large number of tissue
specimens from primary and metastatic carcinomas of the colon
and the ovary will be screened for the presence of amplified DNA
using the newly developed assay.  A series of cell lines, derived
from colon carcinomas and melanomas and passaged as primary or
metastatic tumors in nude mice, will also be tested for the
presence of amplified DNA sequences.  Tumor samples found to
contain amplified DNA sequences will be tested for amplification
of known oncogenes, and oncogene amplification will be
correlated with type and grade of the tumor.  DNA preparations
that contain amplified sequences unrelated to known oncogenes
will be analyzed to identify restriction fragments that are likely
to be derived from or to be adjacent to the essential amplified
gene.  Such fragments, containing transcribed DNA sequences,
will be cloned.  The resulting clones will be used as probes to
assay for amplification and transcription of corresponding genes
in various tumors. Expression of the cloned sequences will be
correlated with the tumor type, the stage of tumor progression
and clinical history.  Full-length cDNA clones of the tumor-
associated amplified genes will be isolated and sequenced.  cDNA
sequences will be analyzed for homology to other proteins and the
presence of potential functional sites.  The function of the cloned
tumor-associated amplified genes will be analyzed by gene
transfer assays.

## Key facts

- **NIH application ID:** 3178240
- **Project number:** 5R01CA039365-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **SAM.gov UEI:** W8XEAJDKMXH3
- **Principal Investigator:** IGOR B RONINSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $177,541
- **Award type:** 5
- **Project period:** 1985-04-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178240

## Citation

> US National Institutes of Health, RePORTER application 3178240, ISOLATION OF AMPLIFIED GENES FROM HUMAN TUMORS (5R01CA039365-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178240. Licensed CC0.

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