| First Author | Kho AT | Year | 2004 |
| Journal | Genes Dev | Volume | 18 |
| Issue | 6 | Pages | 629-40 |
| PubMed ID | 15075291 | Mgi Jnum | J:89201 |
| Mgi Id | MGI:3039064 | Doi | 10.1101/gad.1182504 |
| Citation | Kho AT, et al. (2004) Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers. Genes Dev 18(6):629-40 |
| abstractText | 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. |
