http://mars.uthscsa.edu/POClab/Cancer/ (PC Press Internet CD, 03/1996)
Welcome to the Peter O'Connell Laboratory Breast Cancer
Information Page
We would like to share some current laboratory results generated by breast cancer researchers in the Departments of Pathology and Medicine (Division of Oncology) at the UT Health Science Center at San Antonio. For your convenience, we have also identified additional breast
cancer links on the World Wide Web.
Our interest in the field of breast cancer research centers upon the relationship between pre-malingnant breast lesions (i.e., benign ductal hyperplasia and dysplasia) and invasive breast cancer. We want to determine whether a subset of these "benign" lesions are in fact precursors to invasive breast cancer. If so, we hope to develop methods for identifing these pre-cancerous breast lesions, and hence to establish a means of identifying which patients may require treatment at the pre-malignant stage.
Current Publications . To read a particular article, click on its name. (Check back periodically: we will be adding new papers shortly.)
- V. Pekkel, M.C. Schmitz, Y.-Y. Yu, C. K Osborne, D.C. Allred, P. O'Connell. DNA isolation and pre-amplification from microdissected paraffin-embedded tissues for loss of heterozygosity studies. Submitted to BioTechniques.
- We are studying potential precursor lesions of
invasive breast cancer (i.e. typical hyperplasia, atypical
hyperplasia, and in situ cancer) which commonly show a loss of heterozygosity. In this procedure, samples for DNA extraction are microdissected from formalin-fixed, paraffin-embedded archival tissue samples. These preparations permit efficient PCR amplification of highly polymorphic microsatellite polymorphisms for genetic analysis. However, the variable yields of DNA from particularly small lesions have made extensive testing of these samples difficult. In order to equalize the recovery of DNA from the various morphologically defined lesions and from normal tissue, we have implemented the method of primer-extension pre-amplification (PEP).
To test the fidelity of the PEP technique in this
application, we selected a series of 23 normal/lesion DNA sets
from formalin-fixed, paraffin-embedded tissues. These samples
were analyzed for loss of heterozygosity by direct PCR
amplification with highly polymorphic microsatellite markers, both
before and after the PEP step, to determine its effectiveness. Nearly all of the samples amplified and showed the same patterns of LOH before and after PEP for the eight microsatellite loci assayed.
- Peter O'Connell, Vladimir Pekkel, Suzanne A. W. Fuqua,
C. Kent Osborne, and D. Craig Allred. Molecular genetic studies of early breast cancer evolution. Breast Cancer Research and Treatment, 32: 5-12, 1994.
- In the past few years, there has been an explosion in the number of patients diagnosed with hyperplastic breast disease and in situ breast cancer. Based on epidemiological data, these morphologically defined lesions may be categorized as follows: those with little malignant potential (e.g. typical hyperplasia or proliferative disease without atypia [PDWA]), those with significant malignant potential which may already be "initiated" (e.g. atypical ductal hyperplasia [ADH]), and those which are early "transformed," malignant lesions, but which are not yet invasive (e.g. ductal carcinoma in situ [DCIS]). These may represent sequential evolutionary stages in the ontogeny of invasive breast cancer. If so, then each morphologically defined stage may result from the accumulation of genetic changes, culminating in a transformed clonal lineage capable of invasion and metastasis. Using loss-of-heterozygosity (LOH) analysis, we are studying the genetic changes associated with these lesions in archival tissue samples.
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This page is maintained by Vladimir Pekkel, mailto: vladimir@mars.uthscsa.edu