GROWTH CONTROL IN PEDIATRIC TUMORS

  • Pleasure, David E (PI)
  • Scher, Charles (PI)
  • Biegel, Jaclyn (PI)
  • Huebner, K.A.Y. (PI)
  • Rauscher, Frank (PI)
  • Emanuel, Beverly S. (PI)
  • Bishayee, Subal (PI)
  • Womer, R. (PI)
  • Ross, Alonza (PI)
  • Rovera, Giovanni (PI)

Project: Research project

Description

A major goal of this proposed program is the analysis, at the
molecular level, of the factors that control growth of the most
common childhood malignancies (leukemias, neuroblastomas and soft
tissue tumors) in order to refine future therapeutic and prognostic
approaches. An additional goal is to define genetic alterations
within somatic cells that contribute to the cancerous phenotype in
naturally occurring pediatric malignancies. Distinct genetic alterations in acute non-lymphocytic leukemia
(ANLL) and in pre-B cell acute lymphocytic leukemias (pre-B-ALL)
will be characterized. These changes will be exploited to monitor
the extent of minimal residual disease of leukemia patients
undergoing chemotherapy. In the case of ANLL with a mutated, and
thus, activated ras oncogene, coupling of the polymerase chain
reaction to generation and selective oligonucleotide screening of
recombinant libraries will be utilized to evaluate the extent of
minimal residual disease before completion of treatment. In the
case of pre-B ALL with the t(9;22) translocation, the structural
alterations involving the bcr-abl fusion product will be
characterized by cDNA cloning and sequencing. This approach will
identify the bcr break point; use of cDNA cloning and sequencing.
This approach will identify the bcr break point; use of suitable
oligonucleotide probes will allow efficient amplification of the
bcr/abl translocation and be useful in detection and quantitation
of residual leukemia cells. Molecular characterization of
chromosomal translocation using inverted field gel electrophoresis,
genomic cloning and chromosomal walking will also be the theme of
the proposed studies in osteosarcomas and rhabdomyosarcomas with
the final aim of identifying those genes responsible for the
malignant progression of these diseases. The same soft tissue tumors, as well as neuroblastomas, will be
utilized to determine the role played by the platelet-derived
growth factor receptor and by the nerve growth factor receptor in
controlling both normal and abnormal cellular growth and
differentiation. In these solid tumors, the ultimate goal is to
understand the contribution of abnormal growth factor receptor
expression in contributing to abnormal cellular growth.
Characterization of these abnormalities may provide clinically
important prognostic variables for these tumors.
StatusFinished
Effective start/end date9/30/887/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Nerve Growth Factor Receptor
Chromosomes, Human, Pair 13
Neuroblastoma
Osteosarcoma
Neuroectodermal Tumors
Alveolar Rhabdomyosarcoma
Nerve Growth Factor
Retinoblastoma
Neoplasms
Germ Cells
Cytogenetics
Rhabdomyosarcoma
Cytogenetic Analysis
Pulsed Field Gel Electrophoresis
DNA
Southern Blotting
Tumor Suppressor Genes
Karyotype
Nerve Growth Factor Receptors
Northern Blotting

ASJC

  • Medicine(all)