Genetic and epigenetic alterations in normal bladder epithelium in patients with metachronous bladder cancer.
Mechanisms for multifocal bladder carcinogenesis remain unclear. To see whether normal mucosa had already acquired genetic or epigenetic changes, we examined loss of heterozygosity (LOH) at 10 microsatellite loci and methylation of the p16(INK4) CpG island in multiple tumors and pathologically normal mucosa in six patients with bladder cancer. Either LOH or methylation was detected in 77% of samples of normal epithelium, and LOH detected in samples of normal epithelium was also observed in most tumor samples. This result indicated that a population of cells in morphologically normal epithelium possessed genetic or epigenetic aberrations in common with bladder cancer, which might provide a ground for multiple tumorigenesis.
Muto
S
S
Department of Urology, Faculty of Medicine, The University of Tokyo, Japan.
Horie
S
S
Takahashi
S
S
Tomita
K
K
Kitamura
T
T
D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D019942:Genes, p16 / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000502:physiology; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D001743:Urinary Bladder / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000502:physiology
D004273:DNA, Neoplasm