The recognition of genetic alterations in the different phases of tumor development helps in the identification of risk and prognostic factors. This knowledge eventually will be useful in further classification of tumors, early detection, treatment choices, and ultimately in prevention programs. The interaction of physical and chemical agents with the DNA can lead to damage, which is corrected by several DNA repair mechanisms. Inadequate restoration results in mutations or genetic rearrangements. In addition, mutations may occur in key molecules involved in cell cycle arrest and/or apoptosis that can lead to a further propagation of the genetic error with the concomitant phenotypic changes. Dr. Orlow coordinates studies undertaken in the Molecular Epidemiology Laboratory, and she collaborates with other investigators of the Epidemiology Service to help elucidate the individual's risk to develop sarcomas, endometrial, colon, liver and oral cancer. Her research focuses mainly on the identification of alterations of the cell cycle, DNA repair genes, and metabolizing genes in individuals with melanomas, bladder tumors, lung cancer, and the evaluation of the individual's overall DNA repair capacity. Dr. Orlow's interests include the identification of polymorphisms involved in the progression of melanoma using novel approaches that involve both the Molecular Epidemiology Laboratory and Computational Biology Center.
Selected Bibliography
Pomerantz J, Schreiber-Agus N, Liegeois NJ, Silverman A, Alland L, Chin L, Potes J, Chen K, Orlow I, Lee HW, Cordon-Cardo C, De Pinho RA. "The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53". Cell 1998;92:713-23.
Orlow I, Drobnjak M, Zhang Z-F, Lewis J, Woodruff JM, Brennan MF, Cordon-Cardo C. "Alterations of the INK4A and INK4B Genes in Adult Soft Tissue Sarcomas: Effect on Survival". J Natl Cancer Inst 1999;91:73-79.
Orlow I, LaRue H, Osman I, Lacombe L, Moore L, Meyer F, Rabbani F, Fradet Y, Cordon-Cardo C. "INK4A and INK4B alterations in Superficial Bladder Tumors". Am J Pathol 1999;11:105-113.
Berwick M, Song Y, Jordan R, Brady MS, Orlow I. Mutagen sensitivity as an indicator of soft tissue sarcoma risk. Environmental and Molecular Mutagenesis 2001;38:223-226.
Berwick M, Orlow I, Hummer AJ, Armstrong BK, Kricker A, Marrett LD, Millikan RC, Gruber SB, Anton-Culver H, Zanetti R, Gallagher RP, Dwyer T, Rebbeck T, Kanetsky PA, Busam K, From L, Mujumdar U, Wilcox H and Begg CB. The Prevalence of CDKN2A Germline Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study. Cancer Epidemiol Biomarkers Prev.; 15:1520-5, 2006.
