Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy.
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Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy. / Kuhlmann, Jan Dominik; Schwarzenbach, Heidi; Otterbach, Friedrich; Heubner, Martin; Wimberger, Pauline; Worm, Karl-Heinz; Kimmig, Rainer; Kasimir-Bauer, Sabine.
in: GENE CHROMOSOME CANC, Jahrgang 50, Nr. 8, 8, 2011, S. 598-605.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Loss of heterozygosity proximal to the M6P/IGF2R locus is predictive for the presence of disseminated tumor cells in the bone marrow of ovarian cancer patients before and after chemotherapy.
AU - Kuhlmann, Jan Dominik
AU - Schwarzenbach, Heidi
AU - Otterbach, Friedrich
AU - Heubner, Martin
AU - Wimberger, Pauline
AU - Worm, Karl-Heinz
AU - Kimmig, Rainer
AU - Kasimir-Bauer, Sabine
PY - 2011
Y1 - 2011
N2 - Disseminated tumor cells (DTC) in the bone marrow (BM) are present in about 35% of ovarian cancers before surgery and after chemotherapy and are associated with worse prognosis. A molecular biomarker in the primary tumor predicting tumor cell spread would be highly desirable. The purpose of the study was to investigate loss of heterozygosity (LOH) in primary ovarian tumors at four ovarian cancer-relevant chromosomal loci involved in apoptosis, platinum sensitivity, or DNA-repair, to assess the prognostic value of LOH and to correlate LOH with DTC occurrence before surgery and after chemotherapy. Primary tumor DNA of 88 patients was analyzed for LOH at four polymorphic microsatellite markers using PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. LOH at the entire marker set correlated with tumor grading (P = 0.0001) and histology (P = 0.004). LOH at marker D10S1765 correlated with FIGO stage (P = 0.046) and grading (P = 0.05), whereas LOH at D17S855 significantly associated with grading (P = 0.023) and histology (P = 0.012), respectively. DTC were detected in 49% of patients before surgery and in 50% of patients after chemotherapy. Interestingly, LOH proximal to D6S1581 significantly correlated with DTC presence before surgery (P = 0.05) and after chemotherapy (P = 0.022). Conclusively, our data suggest that allelic loss at D6S1581 (proximal to M6P/IGF2R locus) serves as a molecular biomarker for the presence of DTC in the BM before and after chemotherapy.
AB - Disseminated tumor cells (DTC) in the bone marrow (BM) are present in about 35% of ovarian cancers before surgery and after chemotherapy and are associated with worse prognosis. A molecular biomarker in the primary tumor predicting tumor cell spread would be highly desirable. The purpose of the study was to investigate loss of heterozygosity (LOH) in primary ovarian tumors at four ovarian cancer-relevant chromosomal loci involved in apoptosis, platinum sensitivity, or DNA-repair, to assess the prognostic value of LOH and to correlate LOH with DTC occurrence before surgery and after chemotherapy. Primary tumor DNA of 88 patients was analyzed for LOH at four polymorphic microsatellite markers using PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. LOH at the entire marker set correlated with tumor grading (P = 0.0001) and histology (P = 0.004). LOH at marker D10S1765 correlated with FIGO stage (P = 0.046) and grading (P = 0.05), whereas LOH at D17S855 significantly associated with grading (P = 0.023) and histology (P = 0.012), respectively. DTC were detected in 49% of patients before surgery and in 50% of patients after chemotherapy. Interestingly, LOH proximal to D6S1581 significantly correlated with DTC presence before surgery (P = 0.05) and after chemotherapy (P = 0.022). Conclusively, our data suggest that allelic loss at D6S1581 (proximal to M6P/IGF2R locus) serves as a molecular biomarker for the presence of DTC in the BM before and after chemotherapy.
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Young Adult
KW - Prognosis
KW - Apoptosis/genetics
KW - Bone Marrow/pathology
KW - DNA, Neoplasm/genetics
KW - Genes, BRCA1
KW - Immunohistochemistry/methods
KW - Loss of Heterozygosity
KW - Microsatellite Repeats/genetics
KW - Ovarian Neoplasms/genetics/pathology
KW - PTEN Phosphohydrolase/genetics
KW - Receptor, IGF Type 2/genetics
KW - Adult
KW - Humans
KW - Aged
KW - Female
KW - Middle Aged
KW - Young Adult
KW - Prognosis
KW - Apoptosis/genetics
KW - Bone Marrow/pathology
KW - DNA, Neoplasm/genetics
KW - Genes, BRCA1
KW - Immunohistochemistry/methods
KW - Loss of Heterozygosity
KW - Microsatellite Repeats/genetics
KW - Ovarian Neoplasms/genetics/pathology
KW - PTEN Phosphohydrolase/genetics
KW - Receptor, IGF Type 2/genetics
M3 - SCORING: Journal article
VL - 50
SP - 598
EP - 605
JO - GENE CHROMOSOME CANC
JF - GENE CHROMOSOME CANC
SN - 1045-2257
IS - 8
M1 - 8
ER -
