CLINICAL SIGNIFICANCE OF GENETIC MARKERS IN COLON CANCER

Project: Research project

Project Details

Description

Colon cancer is one of the most common malignancies in the United States,
afflicting over 160,000 individuals per year. Recently, adjuvant
chemotherapy, given alone for colon cancer or combined with radiation
therapy for rectal cancer, has been demonstrated to be of clinical
utility. Although standard clinical, surgical, and pathologic staging
are available, additional prognostic markers are still critically needed
to more precisely define the subsets of patients who would benefit most
from such therapy. Such prognostic markers may come from our increasing
understanding of the underlying molecular basis of tumor formation in
colorectal cancer. Genetic alterations currently described in colorectal
cancer include the activation of oncogenes and the inactivation of tumor
suppressor genes. However, more recent unpublished data from our
laboratory suggests the presence of a novel genetic mechanism of
tumorigenesis which, unlike those previously described, results in
genetic instability of certain chromosomal elements. Based on a variety
of observations, tumors demonstrating this instability appear to be
genetically distinct from the majority of sporadic tumors. These genetic
alterations, as well as those previously described for oncogenes and.
tumor suppressor genes, have the potential to provide additional, and
perhaps even better prognostic discrimination than what is currently
available. Therefore, it is the intent of this proposal to determine the
clinical and pathologic significance of a variety of molecular genetic
changes that occur in colorectal cancer. These include: a) the
evaluation of unstable DNA elements; and b) loss of heterozygosity for
chromosomes 5, 8, 17, and 18 as the primary targets and 1, 14, and 22 as
the secondary targets. To accomplish these goals, paraffin embedded
material from approximately 700 well-characterized patients, who have
undergone surgery for colorectal cancer and who were followed
prospectively on formal surgical adjuvant treatment protocols, will be
examined. Both genomic instability and loss of heterozygosity will be
assayed simultaneously with the use of PCR-based assays directed toward
the identification microsattelites (also known as (CA)n repeats). For
the initial studies, a minimum of 10 separate (CA)n repeats will be
examined, two each for chromosomes 5, 8, 15, 17, and 18.
StatusFinished
Effective start/end date7/1/931/31/04

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $195,602.00
  • National Institutes of Health
  • National Institutes of Health: $166,265.00
  • National Institutes of Health
  • National Institutes of Health: $201,170.00

ASJC

  • Medicine(all)

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