Abstract
Comparative genomic hybridization (CGH) analyses were performed on 27 human pleural mesothelioma tumour specimens, consisting of 18 frozen tumours and nine paraffin-embedded tumours, to screen for gains and losses of DNA sequences. Copy number changes were detected in 15 of the 27 specimens with a range from one to eight per specimen. On average, more losses than gains of genetic material were observed. The loss of DNA sequences occurred most commonly in the short arm of chromosome 9 (p21-pter), in 60% of the abnormal specimens. Other losses among the abnormal specimens were frequently detected in the long arms of chromosomes 4 (q31.1-qter, 20%), 6 (q22-q24, 33%), 13 (33%),14 (q24-qter, 33%) and 22 (q13, 20%). A gain in DNA sequences was found in the long arm of chromosome 1 (cen-qter) in 33% of the abnormal specimens. Our analysis is the first genome-wide screening for gains and losses of DNA sequences using comparative genomic hybridization in malignant pleural mesothelioma tumours. The recurrent DNA sequence changes detected in this study suggest that the corresponding chromosomal areas most probably contain genes important for the initiation and progression of mesothelioma.
Highlights
MATERIALS AND METHODSThe study was carried out on 27 tumour specimens from patients with malignant pleural mesothelioma
This study is the first Comparative genomic hybridization (CGH) analysis performed on uncultured tumour cells of malignant pleural mesothelioma
In a sample, the reliable detection of ratio changes becomes increasingly difficult (A Kallioniemi et al, 1994). This statement is in agreement with our findings, because we were able to detect changes in the genetic material in most of the paraffin-embedded specimens, in which the malignant cells comprised more than 50% of the sample tissue
Summary
The study was carried out on 27 tumour specimens from patients with malignant pleural mesothelioma. The proportion of tumour tissue in the paraffin-embedded samples, estimated by a pathologist from the Finnish National Mesothelioma Panel after staining the tissue slides with haematoxylin and eosin, ranged from less than 25% to more than 75% (Table 1). The regions in the chromosomes where the ratio exceeded 1.17 or was less than 0.85 were considered overrepresented (gained) or underrepresented (lost), respectively. These cut-off values were based on hybridizations with DNA from the healthy donors (negative controls). A positive control, with known DNA copy number changes (both gains and losses), and a negative control were included in each hybridization as quality controls. P-values were analysed using the Fisher's exact test owing to the small numher of casses
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