RIBSE - Summer Research Institute for Biomedical Materials Science & Engineering

Daniel Stoler, Ph.D. [http://www.roswellpark.org/document_4235_631.html]

Daniel Stoler

Roswell Park Cancer Institute
Department of Cancer Genetics and
Department of Cancer Pathology & Prevention
Phone: 716-845-8610
Email: daniel.stoler@roswellpark.org

The goals of the Stoler laboratory are to understand the role of genomic instability in solid tumor progression and to determine the utility of measurements of genomic instability in the assessment and management of malignant disease. Tumor progression can be envisioned as evolution at a vastly accelerated rate with natural selection favoring the growing tumor mass at the expense of the organism. The tumor must acquire numerous capabilities through gene mutation in order to proliferate and invade. The inadequacy of the normal mutation rate of a cell to produce sufficient numbers of alterations has been demonstrated and underscores the necessity for genome destabilization. Genomic instability is now recognized as one of the hallmarks of neoplastic disease.

Using the genome sampling technique developed in the Stoler laboratory called inter-simple sequence repeat PCR (ISSR-PCR) to study colorectal cancers and polyps, they have found that genomic instability begins early in the course of tumor progression and produces a massive destabilization of the genome. Through the use of other methodologies, including allelotyping, comparative genomic hybridization and spectral karyotyping, they have learned that several independent forms of genomic instability are active in colorectal tumors, which combine to create a highly heterogeneous tumor mass. This laboratory is currently engaged in a search for the genes that underlie genomic instability in all its forms. Finally, the Stoler lab has demonstrated that elevated ISSR genomic instability is associated with poor prognosis in Stage III colorectal cancer patients.

Major research areas of the Stoler laboratory are the analysis of genomic instability in thyroid cancer and the application of measurements of genomic instability to the clinical management of this disease. Nationally, 30% of all thyroid specimens are not diagnosable by fine needle aspiration biopsy and cytology, the current diagnostic standard. Stoler has demonstrated that measurements of genomic instability can distinguish benign from malignant thyroid disease, and thus, could serve to improve diagnosis. The long-term prognosis for patients with well-differentiated, indolent thyroid cancer is excellent, even when factors that represent poor prognostic markers in other cancers are present. Patients with highly aggressive, undifferentiated anaplastic thyroid tumors are not likely to be alive a year after diagnosis. Both diseases arise from the same cell type yet the clinical course of each is very different. The Stoler lab is seeking to learn the reason for this difference. Genomic analyses have revealed that while all forms of genomic instability can be detected in aggressive tumors, differentiated tumors only exhibit the ISSR form. Stoler is currently investigating if this lack of instability serves as the basis for the behavior of differentiated thyroid cancer. In addition, this laboratory is attempting to identify those genes responsible for the onset of aggressive biological behavior by comparing the comparative genomic hybridization patterns of DNA amplifications and deletions detected in aggressive and nonaggressive subtypes of thyroid cancer.