Abstract
Purpose: Seventy percent of all ovarian cancer (OvCa) diseases are diagnosed at an advanced stage due to poor screening methods. In general, the therapy consists of cyto-reductive surgery followed by first line platinum based chemo therapy, which frequently leads to a long-term response. A resistance against platinum therapy was detected in some cases by refractory recurrence within six months after the last donation. Identifying a marker predicting platinum effectiveness could be of great benefit for affected patients.Patients and methods: In this study we propose cyto-genetic procedures identifying markers of platinum resistance. Fresh tumor material was obtained from nine OvCa patients. After the last platinum-based chemotherapy, five patients had refractory recurrence within six month. DNA was isolated from tumor tissues for array-based comparative genomic hybridization (aCGH) analysis. Ten cultured metaphases per case were analyzed by spectral karyotyping (SKY) to detect repeated chromosome rearrangements. The obtained genomic data were correlated to the patients’ clinical follow-up data.Results: Eight chromosome aberrations correlated with recurrence later than six months were detected in tumors by SKY. Further seven chromosome aberrations correlated with a refractory recurrence. Non refractory tumors more frequently showed losses in 19q13.31-q13.42 by aCGH. Tumors with refractory recurrence more frequently showed gains in 17q21.32-17q24.3 and losses in 14q11.2, 9p22-p21.1, and 1p22.3-p22.1. OvCa showed separating cyto-genetic changes differentiated in platinum-refractory and non-refractory cases.Conclusion: Our results suggest that aCGH is the most suitable strategy for this, due to a significantly higher resolution. The loss in 19q13 correlated with better prognosis in OvCa
Highlights
Enormous efforts have been taken in recent years to understand chromosomal aberrations in ovarian cancer (OvCa), the effects on morbity and mortality remain far from satisfactory
Resistance to platinumbased chemotherapy is a significant clinical problem since patients with acquired resistance show a poor outcome in OvCa [14]
Genetic modifications of chromosome 19 in OvCa cells were identified at an early stage of cyto-genetics research [15] and are known to occur in about 20% of the ovarian carcinomas being one of the most frequently reported chromosome with changes in copy number variations [16]
Summary
Enormous efforts have been taken in recent years to understand chromosomal aberrations in ovarian cancer (OvCa), the effects on morbity and mortality remain far from satisfactory. As the chemotherapy with platinum and taxan is still associated with a broad spectrum of serious adverse side effects affecting the general state of health, genetic markers for the prediction of the efficiency of these therapies might help to predict a platinum resistance of the tumor. This could lead to a more personalized therapy sparing inefficient treatment and offering other treatment options
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