Year: 2018
Type: article
Study design: Observational Study
Abstract: 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.
Source: International Journal of Cancer
DOI: 10.1002/ijc.31624
Authors: Sherise D. Ferguson, Siyuan Zheng, Joanne Xiu, Shouhao Zhou, Mustafa Khasraw, Priscilla K. Brastianos, Santosh Kesari, Jethro Hu, Jeremy Rudnick, Michael E. Salacz, David Piccioni, Suyun Huang, Michael A. Davies, Isabella C. Glitza, John V. Heymach, Jianjun Zhang, Nuhad K. Ibrahim, John F. DeGroot, Joseph McCarty, Barbara J. O'Brien, Raymond Sawaya, Roeland G.W. Verhaak, Sandeep K. Reddy, Waldemar Priebe, Zoran Gatalica, David Spetzler, Amy B. Heimberger
Institutions: The University of Texas MD Anderson Cancer Center, Caris Life Sciences (United States), The University of Sydney, Harvard University, Massachusetts General Hospital, Saint John's Health Center, Cedars-Sinai Medical Center, The University of Kansas Cancer Center, University of California San Diego, Moores Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,030
OpenAlex ID: W2809401532