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Profiles of brain metastases: prioritization of therapeutic targets

Ferguson, Sherise D., Zheng, Siyuan, Xiu, Joanne, Zhou, Shouhao, Khasraw, Mustafa, Brastianos, Priscilla K., Kesari, Santosh, Hu, Jethro, Rudnick, Jeremy, Salacz, Michael E., Piccioni, David, Huang, Suyun, Davies, Michael A., Glitza, Isabella C., Heymach, John V., Zhang, Jianjun, Ibrahim, Nuhad K., DeGroot, John F., McCarty, Joseph, O'Brien, Barbara J., Sawaya, Raymond, Verhaak, Roeland G.W., Reddy, Sandeep K., Priebe, Waldemar, Gatalica, Zoran, Spetzler, David and Heimberger, Amy B. 2018, Profiles of brain metastases: prioritization of therapeutic targets, International journal of cancer, vol. 143, no. 11, pp. 3019-3026, doi: 10.1002/ijc.31624.

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Title Profiles of brain metastases: prioritization of therapeutic targets
Author(s) Ferguson, Sherise D.
Zheng, Siyuan
Xiu, Joanne
Zhou, Shouhao
Khasraw, MustafaORCID iD for Khasraw, Mustafa orcid.org/0000-0003-3249-9849
Brastianos, Priscilla K.
Kesari, Santosh
Hu, Jethro
Rudnick, Jeremy
Salacz, Michael E.
Piccioni, David
Huang, Suyun
Davies, Michael A.
Glitza, Isabella C.
Heymach, John V.
Zhang, Jianjun
Ibrahim, Nuhad K.
DeGroot, John F.
McCarty, Joseph
O'Brien, Barbara J.
Sawaya, Raymond
Verhaak, Roeland G.W.
Reddy, Sandeep K.
Priebe, Waldemar
Gatalica, Zoran
Spetzler, David
Heimberger, Amy B.
Journal name International journal of cancer
Volume number 143
Issue number 11
Start page 3019
End page 3026
Total pages 8
Publisher Wiley
Place of publication Chichester, Eng.
Publication date 2018-12-01
ISSN 1097-0215
Keyword(s) DNA repair enzymes
TOP2A
brain metastases
molecular profiling
multiplatform analysis
Summary We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair.
Language eng
DOI 10.1002/ijc.31624
Indigenous content off
Field of Research 1112 Oncology And Carcinogenesis
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution non-commercial licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30114690

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.