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
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.
Available from: John W Park
- "In addition, the genomic aberrations we found in CSFTCs were similar to those frequently observed in primary breast cancers . Furthermore, in the original paper , 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 . 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.
Genomics Data 12/2014; 2:60–62. DOI:10.1016/j.gdata.2014.04.003
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ABSTRACT: Tumor incidence has become higher and higher in recent years, and it has also become the first killer jeopardizing human health. Tumor metastasis is the major barrier for tumor treatment. Some metastases occur in 5 or 10 years and some even in 20 years after tumor is controlled, but the metastases are impossible to defend effectively till now. Therefore, controlling tumor metastasis is critical in determining tumor patients' outcomes. In consideration of the limitations, toxicity and side effects of chemotherapeutic drugs for antitumor metastasis at present stage, seeking for drugs among traditional Chinese medicines (TCM) that share high safety and can effectively prevent and control metastasis is being paid more and more attention. This article is to expound the mechanisms of tumor metastasis and summarize the researches on antitumor metastasis with TCM.
Journal of Cancer Research and Therapeutics 08/2014; 10(Supplement):C20-C26. DOI:10.4103/0973-1482.139748 · 0.79 Impact Factor
Available from: Edward P Furlani
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ABSTRACT: Introduction: The advent of precision medicine will increase the demand for molecular testing on patient tumor specimens. Cytology specimens have been shown to be ideal substrates for molecular testing, but their often paucicellular nature can lead to conflicts in prioritizing sample management. A microfluidic platform was investigated to determine whether cytologic and molecular data could be procured from the same cells, obviating the need for partitioning a sample by multiplexing it instead. Materials and methods: Cytology samples were created from a tissue source, stained with a supravital dye, and enriched using immunomagnetic beads. These cells and the attached immunomagnetic beads were then run through a microfluidic channel, temporarily immobilized for cytologic examination, and then recovered. The cytologic characteristics of these cells was compared with cells from the same source prepared by conventional cytologic preparatory means. DNA was extracted from the cells recovered from the microfluidic channel and the nature of their integrity was assessed. Results: Cytologic features between cells run in a microfluidic channel and prepared by conventional means were similar. The DNA recovered from the cells run through the microfluidic channel was of high molecular weight. Conclusions: Microfluidics enables multiplex testing of cytologic specimens, allowing for cytology-based diagnostic examination and recovery of high-quality DNA. This approach will be of particular benefit for cytology specimens that are paucicellular and will need molecular testing.
01/2015; 4(3). DOI:10.1016/j.jasc.2015.01.007
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