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.
Overview
- The study aims to identify common mechanisms underlying organ development and primary tumor formation in medulloblastomas (MBs) by projecting their gene expression profiles onto a mouse cerebellar development sequence. The hypothesis being tested is that a clinically distinct subset of tumors can be identified by molecular similarity to a precise developmental stage. The methodology used for the experiment includes comparing the outcomes observed under different experimental conditions or interventions detailed in the study, identifying any significant differences or similarities in the results between these conditions, and discussing the key findings of the study and how they relate to the initial hypothesis. The primary objective of the study is to achieve a better understanding of tumor biology and facilitate the generation of relevant cancer models.
Comparative Analysis & Findings
- The study found that 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. The study also found comparable results for human lung cancer vis-a-vis the developing mouse lung, indicating the generalizability of this multiscalar developmental perspective on tumor biology.
Implications and Future Directions
- The study's findings suggest 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. Future research directions could include exploring the implications of these findings for cancer treatment and prevention, identifying other tumor types that exhibit similar developmental patterns, and developing more precise cancer models based on these insights.