Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
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 canc...
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| Format: | Article |
| Language: | en_US |
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American Association for Cancer Research
2017
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| Online Access: | http://hdl.handle.net/1721.1/106521 |
| _version_ | 1811096592671834112 |
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| author | Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven |
| author_sort | Lander, Eric Steven |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T16:46:08Z |
| format | Article |
| id | mit-1721.1/106521 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:46:08Z |
| publishDate | 2017 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/1065212022-10-03T08:11:32Z Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric Steven 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. Massachusetts Institute of Technology. Department of Biology National Institutes of Health (U.S.) (National Human Genome Research Institutes of Health Large-scale Sequencing and Analysis Center. Grant U54 HG003067) 2017-01-18T15:22:26Z 2017-01-18T15:22:26Z 2015-09 2015-08 Article http://purl.org/eprint/type/JournalArticle 2159-8274 2159-8290 http://hdl.handle.net/1721.1/106521 Brastianos, P. K. et al. “Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets.” Cancer Discovery 5.11 (2015): 1164–1177. en_US http://dx.doi.org/10.1158/2159-8290.CD-15-0369 Cancer Discovery Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Lander, Eric Steven Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title | Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title_full | Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title_fullStr | Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title_full_unstemmed | Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title_short | Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets |
| title_sort | genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets |
| url | http://hdl.handle.net/1721.1/106521 |
| work_keys_str_mv | AT landerericsteven genomiccharacterizationofbrainmetastasesrevealsbranchedevolutionandpotentialtherapeutictargets |