Detection and characterization of circulating microsatellite-DNA in blood of patients with breast cancer
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Detection and characterization of circulating microsatellite-DNA in blood of patients with breast cancer. / Schwarzenbach, Heidi; Müller, Volkmar; Stahmann, Nicole; Pantel, Klaus.
In: ANN NY ACAD SCI, Vol. 1022, 01.06.2004, p. 25-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Detection and characterization of circulating microsatellite-DNA in blood of patients with breast cancer
AU - Schwarzenbach, Heidi
AU - Müller, Volkmar
AU - Stahmann, Nicole
AU - Pantel, Klaus
PY - 2004/6/1
Y1 - 2004/6/1
N2 - Increased levels of circulating DNA have been reported in the blood of cancer patients but not healthy individuals. Tumor-specific genomic aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), can be detected in this free extracellular DNA. Identification of these genetic aberrations may play an important role in cancer diagnosis and prediction of disease progression. Moreover, the genomic regions involved might harbor potential targets for therapies. To evaluate the incidence of microsatellite alterations in circulating DNA, we assessed the blood serum of 34 patients with primary (n = 8) and metastatic (n = 24) breast cancer. Samples were also analyzed for the presence of circulating tumor cells using an immunocytological cytokeratin assay, and the concentration of the tumor marker CA 15-3 was determined. Genomic DNA extracted from serum and normal blood leukocytes, as a control, was amplified by the polymerase chain reaction using markers at 4 microsatellite loci of chromosomes 10q22-23, 16q22-23, 17q11-12, and 17q21. In 17 of 34 cancer patients, tumor-specific alterations were detected in serum samples. In 16 patients, LOH at various loci was observed, whereas MSI was only detected in the serum of one patient. The pattern of LOH was very heterogeneous, and LOH was detected at chromosomal loci 10q22-23, 16q22-23, and 17q11-12 but not 17q21. No correlation was found between the detection of circulating tumor DNA and the presence of circulating tumor cells in the blood or serum concentration of CA 15-3. In conclusion, genomic aberrations on chromosomes 10, 16, and 17 are frequent in the circulating DNA of breast cancer patients. However, circulating tumor DNA does not reflect the presence of tumor cells in blood or the level of tumor-associated protein markers such as CA 15-3. Thus, screening for circulating tumor DNA may provide additional diagnostic information.
AB - Increased levels of circulating DNA have been reported in the blood of cancer patients but not healthy individuals. Tumor-specific genomic aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), can be detected in this free extracellular DNA. Identification of these genetic aberrations may play an important role in cancer diagnosis and prediction of disease progression. Moreover, the genomic regions involved might harbor potential targets for therapies. To evaluate the incidence of microsatellite alterations in circulating DNA, we assessed the blood serum of 34 patients with primary (n = 8) and metastatic (n = 24) breast cancer. Samples were also analyzed for the presence of circulating tumor cells using an immunocytological cytokeratin assay, and the concentration of the tumor marker CA 15-3 was determined. Genomic DNA extracted from serum and normal blood leukocytes, as a control, was amplified by the polymerase chain reaction using markers at 4 microsatellite loci of chromosomes 10q22-23, 16q22-23, 17q11-12, and 17q21. In 17 of 34 cancer patients, tumor-specific alterations were detected in serum samples. In 16 patients, LOH at various loci was observed, whereas MSI was only detected in the serum of one patient. The pattern of LOH was very heterogeneous, and LOH was detected at chromosomal loci 10q22-23, 16q22-23, and 17q11-12 but not 17q21. No correlation was found between the detection of circulating tumor DNA and the presence of circulating tumor cells in the blood or serum concentration of CA 15-3. In conclusion, genomic aberrations on chromosomes 10, 16, and 17 are frequent in the circulating DNA of breast cancer patients. However, circulating tumor DNA does not reflect the presence of tumor cells in blood or the level of tumor-associated protein markers such as CA 15-3. Thus, screening for circulating tumor DNA may provide additional diagnostic information.
KW - Breast Neoplasms
KW - Chromosomes, Human, Pair 10
KW - Chromosomes, Human, Pair 16
KW - Chromosomes, Human, Pair 17
KW - Cohort Studies
KW - DNA, Neoplasm
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Keratins
KW - Loss of Heterozygosity
KW - Microsatellite Repeats
KW - Mucin-1
KW - Neoplasm Metastasis
KW - Neoplasm Staging
KW - Polymerase Chain Reaction
KW - Tumor Markers, Biological
U2 - 10.1196/annals.1318.005
DO - 10.1196/annals.1318.005
M3 - SCORING: Journal article
C2 - 15251935
VL - 1022
SP - 25
EP - 32
JO - ANN NY ACAD SCI
JF - ANN NY ACAD SCI
SN - 0077-8923
ER -