FREQUENT LOSS OF HETEROZYGOSITY ON CHROMOSOME 10Q IN MUSCLE-INVASIVE TRANSITIONAL-CELL CARCINOMAS OF THE BLADDER

Loss of heterozygosity (LOH) on chromosome 10 has been observed in sev eral human cancers including glioblastomas, meningiomas, melanomas and endometrial and prostate carcinomas, We have investigated the inciden ce of LOH on chromosome 10 in 36 human transitional cell carcinomas (T CCs) of the bladder, three upper urinary tract TCCs and one lymph node metastasis, using a panel of 27 highly polymorphic markers spanning 1 0p (short arm) and 10q (long arm), Fourteen bladder tumours (39%), the three upper urinary tract tumours and the lymph node metastasis showe d LOH for at least one locus on chromosome 10, Remarkably, LOH on chro mosome 10 was observed mainly in muscle-invasive (P=0.01) and high gra de tumours (P=0.03). For five tumours and the lymph node metastasis, L OH was found at all informative loci, indicating monosomy or isodisomy of chromosome 10, The deletion mapping of the tumours with partial lo ss delineated two minimal regions of loss on chromosome 10q, One regio n, the most telomeric, was bounded by markers D10S214 and D10S169 and the other, the most proximal, was bounded by markers D10S222 and D10S5 31, Our results demonstrate that chromosome 10q LOH is common in muscl e-invasive bladder cancers and that two potential tumour suppressor lo ci, at 10q24.1-q24.3 and 10q26.1-q26.2, may contribute to the malignan t progression of these tumours. Localization of the smallest common re gions of loss in bladder tumours provides a starting point for the ide ntification of the genes involved.