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Transcription profiling of mouse P5 cerebellum to investigate conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of neuroblastoma


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. Experiment Overall Design: Time series with technical (split aliquots) replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Alvin Kho 

PROVIDER: E-GEOD-14514 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Kho Alvin T AT   Zhao Qing Q   Cai Zhaohui Z   Butte Atul J AJ   Kim John Y H JY   Pomeroy Scott L SL   Rowitch David H DH   Kohane Isaac S IS  

Genes & development 20040301 6


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 w  ...[more]

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