# HEPATOCELLULAR CARCINOGENESIS

> **NIH NIH R01** · JACKSON LABORATORY · 1993 · $80,750

## Abstract

The genetic changes which lead to development of primary hepatocellular
carcinoma (PHC) remain enigmatic, although several possible etiologic
agents have been identified.  The major goal of this proposal is to
investigate the genetic changes common to PHC of different etiologies in
an effort to understand development of this disease.  Our previous
investigations pointed to consistent translocations and deletions of
chromosome 1 in hepatoma-derived cells.  Comparison of genomic DNA
obtained from tumor cells and normal cells from the same patient using
"RFLP probes" which map to distal 1p revealed loss of genetic
heterozygosity in the tumor cell.  On the basis of these preliminary
data, we hypothesize that the loss of a tumor suppressor gene is a likely
and possibly initiating step in PHC.  Our proposal is geared to
substantiating this chromosome 1-encoded genetic change in PHCs of
multiple origins and to defining how this and the genetic changes
described by others may lead to PHC.  To accomplish this, we will look
for genetic instability and chromosome loss in premalignant livers and
will transfer individual normal human chromosomes into different
hepatoma-derived cell lines to determine if they suppress tumor cell
growth or tumorigenicity.  To verify our hypothesis of the importance of
1p loss of heterozygosity, we will extend our study to tissue from more
patients and to other probes in order to pinpoint the region containing
the putative suppressor gene, a prerequisite for its cloning.

## Key facts

- **NIH application ID:** 3175031
- **Project number:** 7R01CA037225-10
- **Recipient organization:** JACKSON LABORATORY
- **SAM.gov UEI:** XR6LMXNKDJJ1
- **Principal Investigator:** BARBARA B KNOWLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $80,750
- **Award type:** 7
- **Project period:** 1984-06-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175031

## Citation

> US National Institutes of Health, RePORTER application 3175031, HEPATOCELLULAR CARCINOGENESIS (7R01CA037225-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175031. Licensed CC0.

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