Molecular Profiling of Tumor Cells in Cerebrospinal Fluid and Matched Primary Tumors from Metastatic Breast Cancer Patients with Leptomeningeal Carcinomatosis

Hematology/Oncology, University of California San Francisco.
Cancer Research (Impact Factor: 9.33). 10/2013; 73(23). DOI: 10.1158/0008-5472.CAN-13-2051
Source: PubMed


Although leptomeningeal carcinomatosis is a well-established clinical syndrome, virtually nothing is known about the tumor cells responsible for this particularly aggressive metastatic process. To isolate cerebrospinal fluid-derived tumor cells ("CSFTCs") from 15 metastatic breast cancer patients diagnosed with leptomeningeal carcinomatosis, CSF samples were subjected to a two-step method involving immunomagnetic enrichment and fluorescence-activated cell sorting (IE/FACS), a technique previously used for isolating circulating tumor cells (CTCs) from blood. CSFTCs were subjected to genome-wide copy number analysis by array comparative genomic hybridization. Genomic profiling was successfully performed for 13 of the 15 patients (87%). Copy number analysis in CSFTCs revealed genomic alterations commonly observed in primary breast cancer and CTCs, indicating their malignant origin. Interestingly, 12 (92%) harbored high-level gains on the 8q24 locus, which includes the MYC oncogene. Comparison of CSFTCs against corresponding archival primary tumors in six patients revealed clonal relationships with some divergence. Good concordance among serial samples attested to the reproducibility of the assay. Our approach for isolation and molecular analysis of CSFTCs yielded new insights into the molecular nature of these cells. Further genomic and functional analyses may help elucidate mechanisms by which tumor cells metastasize to the central nervous system.

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    • "In addition, the genomic aberrations we found in CSFTCs were similar to those frequently observed in primary breast cancers . Furthermore, in the original paper [1], we demonstrated the clonal relationship of CSFTCs and their corresponding primary tumors. Interestingly, we found more copy number alterations in CSFTCs as compared to the latter, suggesting the acquisition of additional aberrations in CSFTCs or that less normal DNA contamination was present in our CSFTC samples. "
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    ABSTRACT: A debilitating complication of breast cancer is the metastatic spread of tumor cells to the leptomeninges or cerebrospinal fluid (CSF). Patients diagnosed with this aggressive clinical syndrome, known as leptomeningeal carcinomatosis, have very poor prognosis. Despite improvements in detecting cerebrospinal fluid tumor cells (CSFTCs), information regarding their molecular biology is extremely limited. In our recent work, we utilized a protocol previously used for circulating tumor cell isolation to purify tumor cells from the CSF. We then performed genomic characterization of CSFTCs as well as archival tumors from the same patient. Here, we describe the microarray data and quality controls associated with our study published in the Cancer Research journal in 2013 [1]. We also provide an R script containing code for quality control of microarray data and assessment of copy number calls. The microarray data has been deposited into Gene Expression Omnibus under accession # GSE46068.
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