Susanne M. Gollin, Ph.D.
Departments of Human Genetics, Otolaryngology, and Pathology, University of Pittsburgh Graduate School of Public Health, the Oral Cancer Center at the University of Pittsburgh, and the University of Pittsburgh Cancer Institute, 130 DeSoto Street, Pittsburgh, PA 15261.
(Tel: 412-624-5390 Fax: 412-624-3020 Email: sgollin@helix.hgen.pitt.edu )
Oral squamous cell carcinomas (OSCC) are characterized by complex, hyperploid karyotypes with structural and numerical variations superimposed on clonal chromosomal aberrations [Gollin (2001) Head & Neck 23:238-253]. This chromosomal instability is most likely due to l) structural alterations in the chromosomes and/or mitotic machinery, resulting in abnormal chromosome segregation and propagation of structural chromosome abnormalities and 2) defects in cell cycle regulation, preventing the recognition and correction of segregational errors. We will address the first point. We used classical and molecular cytogenetic analysis by FISH and spectral karyotyping combined with immunohistochemistry to study the chromosomal segregation defects in cultured OSCC cells [Saunders et al. (2000) Proc Natl Acad Sci USA 97:303-308]. Multipolar spindles and lagging chromosomes are common in oral cancer cells during metaphase and anaphase, suggesting defects in the mitotic apparatus and chromosome attachment to it. Dicentric anaphase chromatin bridges are also observed. Gene amplification, especially at band 1 lq 13, and structurally altered chromosomes with constant and variable regions suggest the occurrence of breakage-fusion-bridge (BFB) cycles. These BFB cycles appear to play a role in gene amplification at band 1 lq 13 [Shuster et al. (2000) Genes Chromosomes Cancer 28: 153-163]. We are examining the structure and mechanism of 1lq13 amplification using molecular genetic methodologies including quantitative microsatellite analysis (QuMA) [Ginzinger et al. (2000) Cancer Res. 60:5405-5409]. Some of the anaphase bridges persist into telophase, Ieading to micronucleus formation. These results suggest that cytoskeletal defects and BFB cycles may give rise to some of the chromosomal instability in oral cancer cells.
References:
(1) Gollin, S.M. (2001) Chromosomal Alterations in Squamous Cell Carcinomas of the Head and Neck: Window to the Biology of Disease. Head & Neck 23:238-253.
(2) Saunders, W.S., Shuster, M., Huang, X., Gharaibeh, B., Enyenihi, A.H., Petersen, I., & Gollin, S.M. (2000) Chromosomal instability and cytoskeletal defects in oral cancer cells. Proc. Natl. Acad. Sci. USA 97:303-308.
(3) Shuster, M., Han, L., LeBeau, M.M., Davis, E., Sawicki, M., Lese, C.M., Park, N-H., Colicelli, J., & Gollin, S.M. (2000) A consistent pattern of RIN 1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage-fusion-bridge cycle model for 1 lq 13 amplification. Genes Chromosomes Cancer 28: 153-163.
(4) Ginzinger, D.G., Godfrey, T.E., Nigro, J., Moore, D., Pallavicini, M.G., & Jensen, R.H. (2000) Measurement of DNA copy number at microsatellite loci using quantitative real time PCR analysis. Cancer Res. 60:5405-5409.
Susanne M. Gollin, Ph.D. 1974 B.A. Northwestern University, Evanston, IL
1975 M.S. Northwestern University, Evanston, IL
1980 Ph.D. Northwestern University, Evanston, IL
1979-81 Post.doc Univ, Rochester Medicine & Dentistry, NY
PROFESSIONAL EXPERIENCE
1981-1953 Postdoctoral Research Associate, Department of Cell Biology, Baylor College of Medicine, Houston, TX; Advisor: Wayne Wray, Ph.D.
1983-1984 Postdoctoral Research Associate, Robert J. Kleberg Cytogenetics and Prenatal Diagnosis Laboratory, Department of Medicine, Baylot College of Medicine, Houston, TX; Advisor: David H. Ledbetter, Ph.D.
1984-1987 Assistant Professor of Pathology and Pediatrics, University of Arkansas for Medical Sciences and Director, Cytogenetics Laboratory, Little Rock, AR
1997 Diplomate, Clinical Cytogenetics, American Board of Medical Genetics
1987-1995 Assistant Professor of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA
1987-present Member, University of Pittsburgh Cancer Institute, Pittsburgh, PA
1988-1999 Director, The University of Pittsburgh Clinical Cytogenetics Laboratory
1989-present Director, University of Pittsburgh Cancer Institute Cytogenetics Facility
1992-present Member, Allegheny County Board of Health; Vice Chair 1997, 2000
1993 Founding Fellow, American College of Medical Genetics
1994-2000 Member, Clinical Laboratory, Improvement Advisory Committee, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services
1995-present Associate Professor of Human Genetics (with tenure), University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA
1997 Ad Hoc Member, Oral Biology and Medicine I Study Section, National Institutes of Health
1997-present Associate Professor of Pathology, University of Pittsburgh School of Medicine
1997-present Consultant, Immunology Devices Panel, Medical Devices Advisory Committee, Center for Devices and Radiological Health, Food and Drug Administration, U.S. Department of Health and Human Services
1998-present Associate Professor of Otolaryngology, University of Pittsburgh School of Medicine
1999-present Director of Research and Clinical Cytogenetics Consultant, Pittsburgh Cytogenetics Laboratory
1999-present Program Leader, Molecular Carcinogenesis and Cell Biology Program of the Oral Cancer Center at the University of Pittsburgh
Dec., 2000 Member, Ad Hoc Study Section for review of (1) Comprehensive Minority Institution/Cancer Center Partnership (U54); (2) Planning Grant for Minority Institution/Cancer Center Collaboration (P20); and (3) Cooperative Planning Grant for Comprehensive Minority Institution/Cancer Center Partnership (U56) proposals, National Cancer Institute.
Dec.. 2000 Member. Ad Hoc Special Genetics Study Section. NIH.