# SOMATIC GENETIC ALTERATIONS IN GASTROINTESTINAL CANCER

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF BIOLOGICAL RES · 1993 · $137,987

## Abstract

We have adapted a DNA fingerprinting approach to detect tumor specific
genomic differences. The approach is based in the comparison of the genome
fingerprints of normal and tumor tissues from the same individuals, after
the amplification of DNA sequences by the Arbitrary Priming Polymerase
Chain Reaction (AP-PCR). The method is able to detect in a single and
simple experiment, both quantitative and qualitative genomic differences
associated with neoplastic transformation. It also allows the cloning in
a single step of these altered DNA sequences, including those deleted in
the tumor cells.

We propose to use this approach as a molecular alternative to the
cytogenetic analysis of solid tumors; to estimate the extent and compare
the spectrum of genetic alterations occurring in diverse tumors of the
digestive tract at different stages of tumor progression; to explore its
potential value as prognostic indicator for Cancer of the colon and
rectum; and to search for unknown cancer genes in colorectal and other
gastrointestinal tumors.

We will test the hypothesis that the relative values of genetic damage
obtained by the AP-PCR method reflect the degree of aneuploidy of the
cancer cells, and that this information might have value for cancer
diagnosis and prognosis. The existence of uncharacterized cancer genes
involved in the development and/or progression of defined gastrointestinal
neoplasms will be searched by isolating and characterizing the chromosomal
localization of DNA sequences representing recurrent genetic alterations
in these tumors.

Genetic alterations will be identified in a panel of about 200 tumors of
the gastrointestinal tract including adenomas and carcinomas of the colon
and rectum, pancreas and stomach, by comparison of the AP-PCR patterns of
tumor versus normal tissues. Genomic alterations specific to the
metastatic process of any of these tumors will be searched by comparing
primary versus metastatic tumors by the same approach (specific aim 1).

We will continue the follow-up of a subset of these tumors (about 100
colorectal carcinomas), which have been already followed for an average of
over 3 years for recurrence and survival. These tumors have been already
characterized for mutations in the ras oncogene and in the p53 tumor
suppressor gene. The relative values of genetic damage obtained for these
colorectal carcinomas by the AP-PCR method will be correlated with ras and
p53 gene mutations and recurrence and survival rates (specific aim 2).

The chromosomal localization of DNA fragments corresponding to recurrent
tumor specific genetic alterations will be determined by AP-PCR
amplification of panels of human/hamster cell hybrids. When appropriate,
these DNA fragments will be cloned and sequenced to further characterize
by standard PCR approaches their chromosomal localization and their
presence and frequency in other tumors (specific aim 3).

## Key facts

- **NIH application ID:** 3176649
- **Project number:** 2R01CA038579-10A1
- **Recipient organization:** CALIFORNIA INSTITUTE OF BIOLOGICAL RES
- **Principal Investigator:** MANUEL PERUCHO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $137,987
- **Award type:** 2
- **Project period:** 1988-09-30 → 1998-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176649

## Citation

> US National Institutes of Health, RePORTER application 3176649, SOMATIC GENETIC ALTERATIONS IN GASTROINTESTINAL CANCER (2R01CA038579-10A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176649. Licensed CC0.

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