Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31

The most common genetic alteration identified in transitional cell carcinom a (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9, How ever, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, i nitial low stage TCC of the bladder using a panel of 28 microsatellite mark ers spanning chromosome 9 at an average distance of 5 Mb, following a prime r-extension preamplification (PEP) technique. Sixty-seven (48%) tumors show ed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only five (4%) tumors. Deletion s were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with superficial papillary tumors. Combined da ta from the cases with partial 9q deletions displayed four candidate region s for tumor suppressor loci, based on the frequency of deletion observed an d tumors with unique deletions at these sites. In two tumors, the unique pa rtial deletion comprised D9S12 at 9q22.3, a region encompassing loci for th e Gorlin syndrome and multiple self-healing squamous epithelioma gene. In t wo other tumors, the single LOH was identified at the D9S172 locus at 9q31- 32 where the dysautonia and Fukuyama-type congenital muscular dystrophy gen es have been Located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth regi on of deletion was observed at 9q34 between ASS and ABL-I, in two tumors. T his region is frequently deleted in tumors and encompasses the locus for th e hereditary hemorrhagic telangiectasia gene. These findings suggest four t arget regions on 9q within which suppressor genes for TCC may reside.