# C-MYC REARRANGEMENTS IN HUMAN HEMATOPOIETIC NEOPLASIAS

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1991 · $267,633

## Abstract

We and others have demostrated that the chromosomal translocations typical
of Burkl++ lymphomas (BL) and other undifferentiated B-cell lymphomas
(UBL), directly involve the c-myc oncogene locus.  We have characterized
the structural aspects of these translocations and identified different
types of alterations of translocated c-myc alleles in different types of
BL.  Several questions critical for general understanding of the role of
chromosomal translocations in malignancy remain open and will be addressed
in the present research proposal.  In particular, these questions include:
1) Mechanism(s) of chromosomal translocation.  Our preliminary data by
Southern blot analysis suggest that chromosomal translocations may result
from mistakes in either the V-D-J joining (in endemic BL) or class
switching (in sporadic BL) mechanisms of immunoglobulin genes and that
these mistakes involve recombination with different sequences 5' or within
the c-myc locus.  These recombinations and their underlying mechanisms will
be confirmed by cloning and nucleotide sequence analysis of the chromosomal
breakpoints, ii) Mechanism of c-myc gene activation.  We will test whether
structural alterations detectable in translocated c-myc alleles are
sufficient for c-myc activation.  The sequences involved in c-myc
regulation and activation will be identified by comparative analysis of BL
mutants and in vitro constructed mutants in in vitro transformation
assays.  iii) Consequences of c-myc gene activation.  We have preliminarily
shown that high constitutive expression of transfected c-myc genes leads to
an increase of the clonogenic potential of transformed B-cells.  The genes
involved in this phenomenon, i.e.the genes directly or indirectly regulated
by c-myc, will be cloned from cDNA libraries of c-myc transfected cells and
characterized.  iv) Role of c-myc translocation in B-cell transformation in
BL.  A "recapitulation" of the genetic steps involved in BL pathogenesis
will be attempted in vitro, by examing the individual or combined effects
of translocated overexpressed c-myc genes, activated c-ras genes and other
relevant oncogenes in primary human B-cells immortallized by Epstein-Barr
Virus which represents another pathogenetic component of BL.  Biological
effects will be measured by studying morphology, growth factor dependency,
clonagenic properties in semisolid media and tumorigenicity in nude mice.

## Key facts

- **NIH application ID:** 3174932
- **Project number:** 5R01CA037165-08
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** Riccardo Dalla-Favera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $267,633
- **Award type:** 5
- **Project period:** 1984-03-01 → 1992-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174932

## Citation

> US National Institutes of Health, RePORTER application 3174932, C-MYC REARRANGEMENTS IN HUMAN HEMATOPOIETIC NEOPLASIAS (5R01CA037165-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174932. Licensed CC0.

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