Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis.
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.
Björkqvist
A M
AM
Department of Medical Genetics, Haartman Institute, University Helsinki, Finland.
Wolf
M
M
Nordling
S
S
Tammilehto
L
L
Knuuttila
A
A
Kere
J
J
Mattson
K
K
Knuutila
S
S
D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D006801:Humans; D019656:Loss of Heterozygosity; D008654:Mesothelioma / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction