Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers

Genes Dev. 2004 Mar 15;18(6):629-40. doi: 10.1101/gad.1182504.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism*
  • Cerebellum / growth & development
  • Cerebellum / metabolism
  • Down-Regulation
  • Embryo, Mammalian / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Markers
  • Humans
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Up-Regulation

Substances

  • Genetic Markers