Human cancer genetics is a leading edge translational research area at The Ohio State University Medical Center. Studies range from mechanistic studies, which potentially translate into targeted therapy and clinical diagnosis for cancer, to identifying risk factors for cancer. Led by Carlo Croce, MD, and Albert de la Chapelle, MD, PhD, Ohio State’s Human Cancer Genetics Program has placed significant focus on discovering the role of microRNAs in cancer, one of the most exciting recent developments in cancer research. This discovery will revolutionize cancer classification, diagnosis, monitoring, prognosis, and treatment.
MicroRNAs (miRNAs) are small noncoding RNAs of 20-22 nucleotides, which are involved in the regulation of gene expression in critical biological processes, including cell proliferation, differentiation, and apoptosis. MicroRNAs have been implicated in tumorigenesis through function of either tumor suppressor genes or oncogenes.
Croce’s laboratory was the first to identify changes of the expression level of miRNA in chronic lymphocytic leukemia. Subsequently other groups have demonstrated abnormal expression level of miRNA in many types of human tumors. The Croce laboratory developed the oligonucleotide miRNA microarray platform to assess the global expression of miRNA genes in normal and diseased human tissues. Using large scale microarray analysis, the Croce lab found that cancer cells show a distinct miRNA profile compared to normal cells. The technology serves as an important tool in identifying miRNAs as biomarkers, which in turn can be translated into targeted therapies for human cancer.
The de la Chapelle laboratory studies the genetic predisposition of cancer, identifying new genes responsible for colorectal cancer, thyroid cancer, acute myeloid leukemia, and chronic lymphocytic leukemia. His lab has discovered germ-line mutations in the mismatch-repair genes that lead to the development of the Lynch Syndrome, a form of hereditary colorectal cancer. The de la Chapelle lab has subsequently conducted molecular screening of patients with colorectal adenocarcinoma for the Lynch Syndrome. Genetic counseling is offered to the family members of carriers of identified mutations while others who are at risk are tested for mutation. These studies provide early detection for individuals who are at high risk of developing cancer.
References
Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A. Zupo S, Dono M, Dell’Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, and Croce C. MicroRNA profiling reveals distinct signatures in B-cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA, 2004;101(32);11755-11760.
Calin GA, Ferracin M, Cimmino A, DiLeva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, and Croce CM A mircoRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. New Engl J Med, 2005;353(17)1793-1801.
Hampel H, Frankel W, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, and de la Chapelle A Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer). New Engl J Med, 2005;352(18):1851-1860.
He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volina S, Calin G, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, and de la Chapelle A. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA, 2005;102(52):19075-19080.
Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, and Croce CM A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA, 2006;103(7):2257-2261.
Calin GA and Croce CM Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest, 2007;117(8):2059-2066.
To locate more information pertaining to the above referenced articles please visit the PubMed database.