# MOLECULAR PATHOGENESIS OF FOLLICULAR LYMPHOMA

> **NIH NIH R01** · ALLEGHENY UNIVERSITY OF HEALTH SCIENCES · 1992 · $292,819

## Abstract

Follicular lymphoma is one of the few slowly progressing malignancies where
disease evolution can be followed through repeated biopsies.  In a study of
156 patients, we have observed that the majority of patients with
follicular lymphoma and some with diffuse large cell lymphoma have a
characteristic t(14;18)(q32.3;q21.3) chromosome translocation with a bcl-
2/IgH gene rearrangement.  In addition, 1 to 8 of the 20 additional
recurrent chromosome defects were noticed during disease evolution.  Some,
such as duplication 2p and 3p, correlated with cell phenotype or
aggressiveness.  In a few cases we and others have found a combined
t(14;18) and either t(8;14) or t(8;17) with bcl-2 and c-myc rearrangements.
More prevalent chromosomal sites involved in rearrangement include 1p36,
2p13, 3q27, 6q21 and 17q21.  The oncogenes fgr, lck, re1, fim-3, myb, ros,
fyn and bcl-3, have been mapped to these regions.  We plan to use Southern
and Northern blot analysis, pulsed field gel electrophoresis and molecular
cloning, to determine whether some of these genes are altered during the
course of the disease.  To this effect, we have prepared genomic libraries
from lymphoma samples containing either t(3;14)(q27;q32.3) or
t(14;17)(q32.1;q21) to identify the genes affected by these rearrangements.
Southern blot analysis of a patient with 2p13 rearrangements suggest that
the c-rel oncogene, which has not previously been implicated in human
neoplasia, may be the primary gene affected in this region.  We have found
suggestive evidence of c-rel rearrangement or amplification in seven
patients with follicular lymphoma and in one cell line derived from a
diffuse large cell lymphoma with inv ins(2;2)(p13;p15p11.2).  All patients
had very aggressive disease.  In the lymphoma cell line, Southern and
Northern blot analysis, as well as genomic and cDNA cloning, show that the
c-rel oncogene has been truncated at the C-terminus and a hybrid c-rel
message produced.  DNA sequencing of the breakpoint and the fusion message,
followed by expression assays, are planned.  Our long range goal is to
extend these types of studies to other recurrent breakpoints in order to
molecularly characterize the sequential alterations leading to tumor
progression, using follicular lymphoma as a model.

## Key facts

- **NIH application ID:** 3171239
- **Project number:** 5R01CA033314-11
- **Recipient organization:** ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
- **Principal Investigator:** JORGE J YUNIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $292,819
- **Award type:** 5
- **Project period:** 1989-07-01 → 1995-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171239

## Citation

> US National Institutes of Health, RePORTER application 3171239, MOLECULAR PATHOGENESIS OF FOLLICULAR LYMPHOMA (5R01CA033314-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171239. Licensed CC0.

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