Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
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Lander_Genomic characterization.pdf
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1.44 MB
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Checksum (MD5)
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Author(s)
Lander, Eric Steven
Date Issued
September 2015
Journal
Cancer Discovery
Publisher
American Association for Cancer Research
Citation
Brastianos, P. K. et al. “Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets.” Cancer Discovery 5.11 (2015): 1164–1177.
Version
Author's final manuscript
Abstract
Brain metastases are associated with a dismal prognosis. Whether brain metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed wholeexome sequencing of 86 matched brain metastases, primary tumors and normal tissue. In all
clonally related cancer samples, we observed branched evolution, where all metastatic and primary sites shared a common ancestor yet continued to evolve independently. In 53% of cases, we found potentially clinically informative alterations in the brain metastases not detected in the matched
primary-tumor sample. In contrast, spatially and temporally separated brain metastasis sites were genetically homogenous. Distal extracranial and regional lymph node metastases were highly divergent from brain metastases. We detected alterations associated with sensitivity to PI3K/AKT/mTOR, CDK, and HER2/EGFR inhibitors in the brain metastases. Genomic analysis of brain metastases provides an opportunity to identify potentially clinically informative alterations not detected in clinically sampled primary tumors, regional lymph nodes, or extracranial metastases.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1158/2159-8290.CD-15-0369
