Journal
GENES & DEVELOPMENT
Volume 18, Issue 6, Pages 629-640Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1182504
Keywords
cerebellar development; medulloblastoma; comparative genomics; multiscale models; metastasis; principle component analysis
Categories
Funding
- NHLBI NIH HHS [U01 HL066582, HL066582-01] Funding Source: Medline
- NIDDK NIH HHS [R01 DK00837, K12 DK063696] Funding Source: Medline
- NINDS NIH HHS [P01 NS040828, P50 NS040828, R21 NS41764-01, R01 NS35701, R01 NS4051, NS40828-01A1] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available