William G. Kaelin Jr. M.D., professor in the department of medicine at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, associate director for basic research at the Dana-Farber/Harvard Cancer Center and a Howard Hughes Medical Institute investigator. Kaelin’s research interests have focused on tumor suppressor genes and the normal functions of the proteins they encode. The long-term goal of his work is to lay the foundation for the development of new anticancer therapies based on the functions of specific tumor suppressor proteins. His studies of tumor suppressor genes linked to hereditary forms of cancer have uncovered molecular pathways that are important in non-hereditary cancers and have accelerated the development of new treatments for kidney cancer. Kaelin is an elected member of the Institute of Medicine and has served on numerous boards and committees, including the AACR’s Board of Directors, the SU2C Scientific Advisory Committee and the National Cancer Institute (NCI) Board of Scientific Advisors. He has received many awards for his work, including the AACR-Richard and Hinda Rosenthal Prize for Cancer Research, the Paul Marks Prize for Cancer Research from Memorial Sloan-Kettering Cancer Center, the Doris Duke Distinguished Clinical Scientist Award, and the Canada Gairdner International Award.
A summary of the June 2009 article from Dr. Kaelin in Cancer Research is available below:
Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
Rameen Beroukhim, Jean-Philippe Brunet, Arianna Di Napoli, Kirsten D. Mertz, Apryle Seeley, Maira M. Pires, David Linhart, Robert A. Worrell, Holger Moch, Mark A. Rubin, William R. Sellers, Matthew Meyerson, W. Marston Linehan, William G. Kaelin Jr., and Sabina Signoretti
Cancer Res June 1, 2009 69(11):4674–4681
Recent insights into the role of the von-Hippel Lindau (VHL) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of three genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into two groups: one group with genomic profiles highly dissimilar to the majority of ccRCC and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL.