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 several human cancers including glioblastomas, meningiomas, melanomas and endometrial and prostate carcinomas. We have investigated the incidence of LOH on chromosome 10 in 36 human transitional cell carcinomas (TCCs) of the bladder, three upper urinary tract TCCs and one lymph node metastasis, using a panel of 27 highly polymorphic markers spanning 10p (short arm) and 10q (long arm). Fourteen bladder tumours (39%), the three upper urinary tract tumours and the lymph node metastasis showed LOH for at least one locus on chromosome 10. Remarkably, LOH on chromosome 10 was observed mainly in muscle-invasive (P = 0.01) and high grade tumours (P = 0.03). For five tumours and the lymph node metastasis, LOH was found at all informative loci, indicating monosomy or isodisomy of chromosome 10. The deletion mapping of the tumours with partial loss delineated two minimal regions of loss on chromosome 10q. One region, the most telomeric, was bounded by markers D10S214 and D10S169 and the other, the most proximal, was bounded by markers D10S222 and D10S531. Our results demonstrate that chromosome 10q LOH is common in muscle-invasive bladder cancers and that two potential tumour suppressor loci, at 10q24.1-q24.3 and 10q26.1-q26.2, may contribute to the malignant progression of these tumours. Localization of the smallest common regions of loss in bladder tumours provides a starting point for the identification of the genes involved.
Cappellen
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UMR 144, Centre National de la Recherche Scientifique, Institut Curie, Section de Recherche, Paris, France.
Gil Diez de Medina
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Chopin
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Thiery
J P
JP
Radvanyi
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D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D002642:Chick Embryo; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D018450:Disease Progression; D006579:Heterozygote; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D014571:Urologic Neoplasms / Q000235:genetics / Q000473:pathology