Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer
| Autor: | Carolin Lackner, Peter Ulz, Sumitra Mohan, Christin Gasch, Martina Auer, Klaus Pantel, Julie Waldispuehl-Geigl, Jochen B. Geigl, Ellen Heitzer, Gerald Höfler, Eva M. Hoffmann, Gunda Pristauz, Martin Pichler, Oliver Mauermann, Edgar Petru, Heinz Sill, Sabine Riethdorf, Sigurd Lax, Hellmut Samonigg, Florian Eisner, Thomas Bauernhofer, Michael R. Speicher |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty plasma DNA Colorectal cancer Gene Dosage Breast Neoplasms Biology medicine.disease_cause Deep sequencing 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Genotype medicine Cancer Genetics predictive and prognostic biomarker Humans ddc:610 Neoplasm Metastasis 030304 developmental biology Aged Aged 80 and over 0303 health sciences Mutation Cancer High-Throughput Nucleotide Sequencing tumor monitoring DNA Neoplasm Sequence Analysis DNA Middle Aged medicine.disease Neoplastic Cells Circulating Primary tumor Metastatic breast cancer 3. Good health Genes ras Oncology 030220 oncology & carcinogenesis Case-Control Studies copy number changes Female Colorectal Neoplasms Biomarkers |
| Zdroj: | International Journal of Cancer International Journal of Cancer. Journal International du Cancer International Journal of Cancer; Vol 133 |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.28030 |
| Popis: | With the increasing number of available predictive biomarkers, clinical management of cancer is becoming increasingly reliant on the accurate serial monitoring of tumor genotypes. We tested whether tumor-specific copy number changes can be inferred from the peripheral blood of patients with cancer. To this end, we determined the plasma DNA size distribution and the fraction of mutated plasma DNA fragments with deep sequencing and an ultrasensitive mutation-detection method, i.e., the Beads, Emulsion, Amplification, and Magnetics (BEAMing) assay. When analyzing the plasma DNA of 32 patients with Stage IV colorectal carcinoma, we found that a subset of the patients (34.4%) had a biphasic size distribution of plasma DNA fragments that was associated with increased circulating tumor cell numbers and elevated concentration of mutated plasma DNA fragments. In these cases, we were able to establish genome-wide tumor-specific copy number alterations directly from plasma DNA. Thus, we could analyze the current copy number status of the tumor genome, which was in some cases many years after diagnosis of the primary tumor. An unexpected finding was that not all patients with progressive metastatic disease appear to release tumor DNA into the circulation in measurable quantities. When we analyzed plasma DNA from 35 patients with metastatic breast cancer, we made similar observations suggesting that our approach may be applicable to a variety of tumor entities. This is the first description of such a biphasic distribution in a surprisingly high proportion of cancer patients which may have important implications for tumor diagnosis and monitoring. What's new? Tumors shed their DNA into the bloodstream. This DNA can be detected, but whether it's useful as a diagnostic tool hasn't been clear from existing reports. Rather than attempt to pick out specific mutations, however, this study asked whether it would be possible to get a genome-wide view of tumor-specific copy number changes from this circulating tumor cell DNA. When they analyzed the plasma DNA of patients with colorectal cancer, the authors found that about a third of the patients had plasma DNA that fell into two distinct size categories, and this correlated with higher numbers of circulating tumor cells. They could then detect tumor-specific copy-number changes from this plasma DNA. Further developing this non-invasive acquisition of tumor material could aid in tailoring specific disease treatment strategies. |
| Databáze: | OpenAIRE |
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