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

Abstract

Summary Previous molecular cytogenetic studies by comparative genomic hybridization (CGH) on primary tumours of human malignant mesothelioma have revealed that loss of genetic material at chromosome 14q is one of the most frequently occurring aberrations. Here we further verify the frequency and pattern of deletions at 14q in mesothelioma. A high-resolution deletion mapping analysis of 23 microsatellite markers was performed on 18 primary mesothelioma tumours. Eight of these had previously been analysed by CGH. Loss of heterozygosity or allelic imbalance with at least one marker was detected in ten of 18 tumours (56%). Partial deletions of varying lengths were more common than loss of all informative markers, which occurred in only one tumour. The highest number of tumours with deletions at a specific marker was detected at 14q11.1-q12 with markers D14S283 (five tumours), D14S972 (seven tumours) and D14S64 (five tumours) and at 14q23-q24 with markers D14S258 (five tumours), D14S77 (five tumours) and D14S284 (six tumours). We conclude from these data that genomic deletions at 14q are more common than previously reported in mesothelioma. Furthermore, confirmation of previous CGH results was obtained in all tumours but one. This tumour showed deletions by allelotyping, but did not show any DNA copy number change at 14q by CGH. Although the number of tumours allelotyped was small and the deletion pattern was complex, 14q11.1-q12 and 14q23-q24 were found to be the most involved regions in deletions. These regions provide a good basis for further molecular analyses and may highlight chromosomal locations of tumour suppressor genes that could be important in the tumorigenesis of malignant mesothelioma.

CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma—A miRNA microarray analysis

“…As for potential TSGs, miR-34* and miR-429 are located at 1p36 while miR-203 resides at 14q32, which are all well documented to be frequently deleted (Tiainen et al, 1988;Kivipensas et al, 1996;Bjorkqvist et al, 1997;Krismann et al, 2002;Lindholm et al, 2007;Taniguchi et al, 2007). Loss of 14q is common in MM (Balsara et al, 1999;Bjorkqvist et al, 1999;De Rienzo et al, 2000) and as no target gene has yet been identified, one can speculate that miR-203 is that target. As a consequence of miR-203 deletion, its target gene JUN oncogene can carry on its oncogenetic properties without control.…”

The Potential Value of Comparative Genomic Hybridization Analysis in Effusion—and Fine Needle Aspiration Cytology

“…Such obvious chromosomal imbalances favor the diagnosis of a benign or malignant neoplasm and argue against a reactive condition (15,16). In addition, loss of 6q and 22q, as well chromosomes 14 and 22 represent some of the most frequent and tumor-specific genetic imbalances in malignant mesothelioma (17)(18)(19)(20)(21), thus supporting cytologic diagnosis of malignancy (22). In contrast, loss of 22q is a very uncommon CGH finding in non-small-cell lung carcinomas (8,23), a tumor type, which must be distinguished from malignant mesothelioma.…”

Gene copy number analysis in malignant pleural mesothelioma using oligonucleotide array CGH

“…Several studies have been carried out using comparative genomic hybridization (CGH) to detect gene copy number alterations, i.e., losses, gains and amplifications. The most frequently reported aberrations by cytogenetic analyses or conventional CGH (cCGH) are losses at 1p21, 3p, 6q22, 9p21, 10pter ] p13, 13q, 14q, 17pter ] p12, and 22q, and gains at 1q23, 1q32, 3p21, 4p12 ] q13, 4q31 ] q32, 7p15 ] p14, 8q22 ] q23, and 15q22 ] q25 (Tiainen et al, 1989;Bjorkqvist et al, 1997Bjorkqvist et al, , 1998Bjorkqvist et al, , 1999Ascoli et al, 2001;Krismann et al, 2002). Because the resolution of cCGH is limited to chromosomal bands, a gene-level view cannot be obtained.…”