![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH PAPER
1 Children's Hospital Informatics Program, 2 Department of Neurology, and Divisions of 3 Newborn Medicine and 4 Endocrinology, Children's Hospital Boston, Boston, Massachusetts 02115, USA; 5 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA; 6 Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Boston, Massachusetts 02139, USA
Identification of common mechanisms underlying organ development and primary tumor formation should yield new insights into tumor biology and facilitate the generation of relevant cancer models. We have developed a novel method to project the gene expression profiles of medulloblastomas (MBs)—human cerebellar tumors—onto a mouse cerebellar development sequence: postnatal days 1-60 (P1-P60). Genomically, human medulloblastomas were closest to mouse P1-P10 cerebella, and normal human cerebella were closest to mouse P30-P60 cerebella. Furthermore, metastatic MBs were highly associated with mouse P5 cerebella, suggesting that a clinically distinct subset of tumors is identifiable by molecular similarity to a precise developmental stage. Genewise, down- and up-regulated MB genes segregate to late and early stages of development, respectively. Comparable results for human lung cancer vis-a-vis the developing mouse lung suggest the generalizability of this multiscalar developmental perspective on tumor biology. Our findings indicate both a recapitulation of tissue-specific developmental programs in diverse solid tumors and the utility of tumor characterization on the developmental time axis for identifying novel aspects of clinical and biological behavior.
[Keywords: cerebellar development; medulloblastoma; comparative genomics; multiscale models; metastasis; principle component analysis]
Received December 30, 2003; revised version accepted February 25, 2004.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1182504.
7 These authors contributed equally to this work.
8 E-MAIL david_rowitch{at}dfci.harvard.edu; FAX (617) 632-4850.
9 E-MAIL isaac_kohane{at}harvard.edu; FAX (617) 730-0253.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Fan and C. G. Eberhart Medulloblastoma Stem Cells J. Clin. Oncol., June 10, 2008; 26(17): 2821 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Briggs, I. M. Corcoran-Schwartz, W. Zhang, T. Harcke, W. L. Devereux, S. B. Baylin, C. G. Eberhart, and D. N. Watkins Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma Genes & Dev., March 15, 2008; 22(6): 770 - 785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stock, D. Monga, X. Tan, A. Micsenyi, N. Loizos, and S. P.S. Monga Platelet-derived growth factor receptor-{alpha}: a novel therapeutic target in human hepatocellular cancer Mol. Cancer Ther., July 1, 2007; 6(7): 1932 - 1941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Otu, K. Naxerova, K. Ho, H. Can, N. Nesbitt, T. A. Libermann, and S. J. Karp Restoration of Liver Mass after Injury Requires Proliferative and Not Embryonic Transcriptional Patterns J. Biol. Chem., April 13, 2007; 282(15): 11197 - 11204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Inaoka, Y. Fukuoka, and I. S. Kohane Evidence of spatially bound gene regulation in Mus musculus: Decreased gene expression proximal to microRNA genomic location PNAS, March 20, 2007; 104(12): 5020 - 5025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Y. Frank, A. T. Kho, T. Schatton, G. F. Murphy, M. J. Molloy, Q. Zhan, M. F. Ramoni, M. H. Frank, I. S. Kohane, and E. Gussoni Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin J. Cell Biol., October 9, 2006; 175(1): 99 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. T. Gazda, A. T. Kho, D. Sanoudou, J. M. Zaucha, I. S. Kohane, C. A. Sieff, and A. H. Beggs Defective Ribosomal Protein Gene Expression Alters Transcription, Translation, Apoptosis, and Oncogenic Pathways in Diamond-Blackfan Anemia Stem Cells, September 1, 2006; 24(9): 2034 - 2044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Uziel, F. Zindy, S. Xie, Y. Lee, A. Forget, S. Magdaleno, J. E. Rehg, C. Calabrese, D. Solecki, C. G. Eberhart, et al. The tumor suppressors Ink4c and p53 collaborate independently with Patched to suppress medulloblastoma formation Genes & Dev., November 15, 2005; 19(22): 2656 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hu and R. A. Shivdasani Overlapping Gene Expression in Fetal Mouse Intestine Development and Human Colorectal Cancer Cancer Res., October 1, 2005; 65(19): 8715 - 8722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. Oliver, T. A. Read, J. D. Kessler, A. Mehmeti, J. F. Wells, T. T. T. Huynh, S. M. Lin, and R. J. Wechsler-Reya Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma Development, May 15, 2005; 132(10): 2425 - 2439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lepourcelet, L. Tou, L. Cai, J.-i. Sawada, A. J. F. Lazar, J. N. Glickman, J. A. Williamson, A. D. Everett, M. Redston, E. A. Fox, et al. Insights into developmental mechanisms and cancers in the mammalian intestine derived from serial analysis of gene expression and study of the hepatoma-derived growth factor (HDGF) Development, January 15, 2005; 132(2): 415 - 427. [Abstract] [Full Text] [PDF]
|
|
