Editors' ChoiceMEDICINE

Cancer Genomes: From Chaos Comes Order?

Sci. Signal.  30 Sep 2008:
Vol. 1, Issue 39, pp. ec340
DOI: 10.1126/scisignal.139ec340

Identification of the genes altered in cancer cells is critical for understanding how the disease arises and for designing more effective diagnostic tests and therapies. Parsons et al. and Jones et al. catalog the numerous genomic alterations that help turn normal cells into two of the deadliest human cancers: glioblastoma multiforme (the most common type of brain cancer) and pancreatic cancer. Although for each cancer type, the specific genomic alterations varied from tumor to tumor, the altered genes affected a limited number of cellular signaling pathways and regulatory processes, suggesting that these are the pathways that go awry and lead to the disease. Of particular interest in the glioblastoma study was the discovery of recurrent mutations in the active site of isocitrate dehydrogenase 1, encoded by the IDH1 gene. In this small study, IDH1 mutations were more prevalent in glioblastomas from younger patients and in “secondary” glioblastomas, and they were associated with a better prognosis.

D. W. Parsons, S. Jones, X. Zhang, J. C.-H. Lin, R. J. Leary, P. Angenendt, P. Mankoo, H. Carter, I-M. Siu, G. L. Gallia, A. Olivi, R. McLendon, B. A. Rasheed, S. Keir, T. Nikolskaya, Y. Nikolsky, D. A. Busam, H. Tekleab, L. A. Diaz, Jr., J. Hartigan, D. R. Smith, R. L. Strausberg, S. K. N. Marie, S. M. O. Shinjo, H. Yan, G. J. Riggins, D. D. Bigner, R. Karchin, N. Papadopoulos, G. Parmigiani, B. Vogelstein, V. E. Velculescu, K. W. Kinzler, An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807-1812 (2008). [Abstract] [Full Text]

S. Jones, X. Zhang, D. W. Parsons, J. C.-H. Lin, R. J. Leary, P. Angenendt, P. Mankoo, H. Carter, H. Kamiyama, A. Jimeno, S.-M. Hong, B. Fu, M.-T. Lin, E. S. Calhoun, M. Kamiyama, K. Walter, T. Nikolskaya, Y. Nikolsky, J.Hartigan, D. R. Smith, M. Hidalgo, S. D. Leach, A. P. Klein, E. M. Jaffee, M. Goggins, A. Maitra, C. Iacobuzio-Donahue, J. R. Eshleman, S. E. Kern, R. H. Hruban, R. Karchin, N. Papadopoulos, G. Parmigiani, B. Vogelstein, V. E. Velculescu, K. W. Kinzler, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321 1801-1806 (2008).[Abstract] [Full Text]