Assistant Member, Department of Cancer Genetics
Roswell Park Cancer Institute
Phone: 716-845-8610
e-mail: daniel.stoler@roswellpark.org

Assistant Professor, Department of Cancer Pathology & Prevention
Roswell Park Graduate Division, State University of New York at Buffalo

Dr. Daniel L. Stoler joined the staff of Roswell Park Cancer Institute (RPCI) in 1986. He earned his doctoral degree in Cellular and Molecular Biology at the State University of New York at Buffalo (1986) and complete his postdoctoral training at Roswell Park Cancer Institute.

Dr. Stoler's research interests include the role of genomic instability in solid tumor progression. He has authored or co-authored over 90 publications, book chapters and abstracts.

General Research Interest
The goals of my research 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 our laboratory called inter-simple sequence repeat PCR (ISSR-PCR) to study colorectal cancers and polyps, we 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, we’ve learned that several independent forms of genomic instability are active in colorectal tumors, which combine to create a highly heterogeneous tumor mass. We are currently engaged in a search for the genes that underlie genomic instability in all its forms. Finally, we have demonstrated that elevated ISSR genomic instability is associated with poor prognostic marker in Stage III colorectal cancer patients.

An additional focus of the laboratory is the analysis of genomic instability in thyroid cancer. 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 observed. 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. Genomic analyses have revealed that while all forms of genomic instability can be detected in aggressive tumors, indolent differentiated tumors only exhibit the ISSR form. We are currently investigating if this lack of instability serves as the basis for the behavior of differentiated thyroid cancer and if so, we will attempt to identify those genes responsible for the onset of aggressive biological behavior.

Finally, we are exploring the role of genomic instability in cancers and benign lesions of the head and neck. Histologically homogeneous tumors from different head and neck sites, separated by only small anatomical distances, display a wide range of biological behaviors and require different treatment regimens. Our studies seek to determine to role of genomic instability in these behavioral differences. Certain, but not all, benign lesions in the oral cavity have been identified as high risk for progression to malignancy. We are using measurements of genomic instability to determine which lesions are most likely to progress.

Selected Publications

• Stoler, D.L., Chen, N., Kahlenberg, M.S., Basik, M., Petrelli, N.J., Rodriguez-Bigas, M., Petrelli, N.J. and Anderson, G.R. The onset and extent of genomic instability in sporadic colorectal tumor progression.. Proc. Natl. Acad. Sci. 96:15121-15126, 1999.
• Rodriguez-Bigas, M.A., Stoler, D.L, Bertarro, L., Anderson, G.R. and Baba, S. Colorectal cancer: how does it start? How does it metastasize? Surg. Onc. Clin. North Am. 9: 643-652, 2000
• Lipkin, S.M., Wang, V., Stoler, D.L., Anderson, G.R., Kirsch,I., Hadley, D., Lynch, H.T., and Collins, F.R. Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers. Human Mutation 17: 389-396, 2001.
• Anderson, G.R., Stoler, D.L. and Brenner, B.M. Cancer: The Evolutionary Consequence of a Destabilized Genome. BioEssays 23:1037-1046, 2001.
• Anderson, G.R., Brenner, B.M., Swede, H., Chen, N., Henry, W.M., Conroy, J.M., Karpenko, M.J., Issa, J-P., Bartos, J.D., Brunelle, J.K., Jahreis, G.P., Kahlenberg, M.S., Basik, M., Sait, S., Rodriguez- Bigas, M.A., Nowak, N.J., Petrelli, N.J., Shows, T.B. and Stoler, D.L. Intrachromosomal genomic instability in human sporadic colorectal cancer measured by genome-wide allelotyping and inter-(simple sequence repeat) PCR. Cancer Research 61:8274-8283,2001.
• Stoler, D.L., Datta, R.V., Charles, M.A., Block, A.W., Brenner, B.M., Sieczka, E.M., Hicks, Jr., W.L., Loree, T.R. and Anderson, G.R. Genomic Instability Measurement in the Diagnosis of Thyroid Neoplasms. Head and Neck 24:290-295, 2002.
• Wiseman, S.M., Loree, T.R., Hicks, Jr., W.L., Rigual, N.R., Winston, J.S., Tan, D., Anderson, G.R., Stoler, D.L. Anaplastic Thyroid Cancer Evolved From Papillary Carcinoma: Demonstration Of Anaplastic Transformation Utilizing The Inter-simple Sequence Repeat Polymerase Chain Reaction. Archives of Otolaryngology: Head and Neck Surgery 129:96-100, 2003.
• Wiseman, S.M., Loree, T.R., Hicks, Jr., W.L., Douglas, W., Rigual, N.R., Anderson, G.R., Stoler, D.L. Anaplastic transformation of thyroid cancer: Review of clinical, pathological, and molecular evidence provides new insights into disease biology and future therapy. Head and Neck 25:662-670, 2003.
• Wiseman, S.M., Loree, T.R., Rigual, N.R., Hicks, Jr., W.L., Winston, J.S., Swede, H., Bartos, J.D., Anderson, G.R., Stoler, D.L. Papillary Thyroid Cancer: High Inter-(Simple Sequence Repeat) Genomic Instability In A Typically Indolent Cancer. Head and Neck 25:825-832, 2003.
• Wiseman S.M., Stoler, D.L., Anderson, G.R., Hicks, Jr., W.L., Rigual, N.R., Swede, H., Tan, D., Loree T.R. Squamous Cell Carcinoma Of The Head And Neck In Nonsmokers And Nondrinkers: An Analysis of Clinicopathologic Factors And Treatment Outcomes. Surgical Oncology, 10:551-557, 2003.