Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets

By P. Brastianos, Scott L. Carter, S. Santagata, D. Cahill, A. Taylor-Weiner, Robert Jones, E. V. Van Allen, M. Lawrence, Peleg Horowitz, Kristian Cibulskis and 34 more. Cancer Discovery, 2015

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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 whole-exome 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.

Subfields: Genetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/21e131b59e4000ad741f23df45e107a641fd7af2

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In Pulmonary and Respiratory Medicine

Citations in the corpus

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The PI3K pathway in human disease (2017, neutral): “Parallel genomic analyses of 86 diverse, primary tumors and brain metastases from individual patients revealed that more than half of brain metastases contained actionable mutations not seen in the corresponding primary tumor (Brastianos et al., 2015).”
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