Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer
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Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer. / Heitzer, Ellen; Auer, Martina; Hoffmann, Eva Maria; Pichler, Martin; Gasch, Christin; Ulz, Peter; Lax, Sigurd; Waldispuehl-Geigl, Julie; Mauermann, Oliver; Mohan, Sumitra; Pristauz, Gunda; Lackner, Carolin; Höfler, Gerald; Eisner, Florian; Petru, Edgar; Sill, Heinz; Samonigg, Hellmut; Pantel, Klaus; Riethdorf, Sabine; Bauernhofer, Thomas; Geigl, Jochen B; Speicher, Michael R.
In: INT J CANCER, Vol. 133, No. 2, 15.07.2013, p. 346-56.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer
AU - Heitzer, Ellen
AU - Auer, Martina
AU - Hoffmann, Eva Maria
AU - Pichler, Martin
AU - Gasch, Christin
AU - Ulz, Peter
AU - Lax, Sigurd
AU - Waldispuehl-Geigl, Julie
AU - Mauermann, Oliver
AU - Mohan, Sumitra
AU - Pristauz, Gunda
AU - Lackner, Carolin
AU - Höfler, Gerald
AU - Eisner, Florian
AU - Petru, Edgar
AU - Sill, Heinz
AU - Samonigg, Hellmut
AU - Pantel, Klaus
AU - Riethdorf, Sabine
AU - Bauernhofer, Thomas
AU - Geigl, Jochen B
AU - Speicher, Michael R
N1 - Copyright © 2013 UICC.
PY - 2013/7/15
Y1 - 2013/7/15
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Biological Markers
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Colorectal Neoplasms
KW - DNA, Neoplasm
KW - Female
KW - Gene Dosage
KW - Genes, ras
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation
KW - Neoplasm Metastasis
KW - Neoplastic Cells, Circulating
KW - Sequence Analysis, DNA
U2 - 10.1002/ijc.28030
DO - 10.1002/ijc.28030
M3 - SCORING: Journal article
C2 - 23319339
VL - 133
SP - 346
EP - 356
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 2
ER -