Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma

Abstract

Summary 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.

Comparison of DNA copy number changes in malignant mesothelioma, adenocarcinoma and large-cell anaplastic carcinoma of the lung

“…The DNA copy number changes detected in mesothelioma in this analysis, such as losses of genetic material in lp, 4q, 6q, 9p, 13q, 14q and gains in 5p and 7p, are supported by previous cytogenetic and CGH studies, although with some differences in frequency of occurrence (Tiainen et al, 1989;Hagemeijer et al, 1990;Taguchi et al, 1993;Kivipensas et al, 1996;Bjorkqvist et al, 1997). These chromosomal regions probably carry important genes for the development and progression of mesothelioma.…”

Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis

“…In eight of the tumours (nos 1, 2, 3, 4, 10, 13, 14 and 15) we were able to compare the allelotyping results with previous CGH data of 14q (Björkqvist et al, 1997(Björkqvist et al, , 1998. Loss of genetic material at 14q was found by CGH in tumour nos 1, 3, 4 and 15.…”

“…Fifty-six per cent of the tumours displayed a deletion. The percentage is much higher than that (24%) observed in primary tumours by CGH (Kivipensas et al, 1996;Björkqvist et al, 1997Björkqvist et al, , 1998. However, this is not unexpected due to the small partial deletions observed by allelotyping in some of the tumours and because of the resolution limitation of the CGH method (Kallioniemi et al, 1994).…”

“…Tumours homozygous for a specific locus were defined as uninformative. LOH was observed in heterozygous samples when one of the alleles in the tumour D14S72 D14S1003 D14S283 D14S972 D14S64 D14S80 D14S1060 D14S75 D14S269 D14S66 D14S63 D14S258 D14S277 D14S77 D14S71 D14S284 D14S76 D14S74 D14S68 D14S81 D14S65 D14S78 Björkqvist et al (1998) respectively; i,j cases 4 and 14 in Björkqvist et al (1997) respectively; k genetic distance between markers in cM; s s = Retained heterozygosity; s = LOH; s ss = Al; -= Uninformative; ND = Not determined; X = no data Table 1 Pattern and frequency of loss of heterozygosity (LOH) and allelic imbalance (AI) detected with 23 microsatellite markers at 14q in 18 primary mesothelioma tumours Tumour a DNA was reduced in intensity relative to the remaining allele and the alleles in the normal DNA. Other intensity differences were interpreted merely as AIs.…”

“…However, no aberration specific to mesothelioma has been detected. Comparative genomic hybridization (CGH) analyses on primary mesothelioma tumours and cell lines have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations (Kivipensas et al, 1996;Björkqvist et al, 1997Björkqvist et al, , 1998Balsara et al, 1999). In this study we further verify the frequency and pattern of deletions at 14q in primary mesothelioma tumours using polymerase chain reaction (PCR) and 23 microsatellite markers spanning the whole of the long arm of chromosome 14.…”