DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas.
OBJECTIVE
DNA methylation has important roles in genomic stability. Accordingly DNA hypomethylation on pericentromeric satellite regions may induce chromosomal instability through heterochromatin decondensation and chromosomal recombination enhancement. We elucidated the significance of aberrant DNA methylation on pericentromeric satellite regions during urothelial carcinogenesis.


METHODS
We examined DNA methylation status on satellites 2 and 3 by Southern blotting and determined the allelic status of chromosome 9 using 6 microsatellite markers (D9S775, D9S925, D9S304, D9S303, D9S283 and D9S747) in 27 transitional cell carcinomas of the bladder, ureter or renal pelvis and corresponding noncancerous tissues.


RESULTS
DNA hypomethylation on satellites 2 and 3 was detected in 2 (7%) and no (0%) noncancerous tissues, and in 11 (41%) and 12 (44%) urothelial carcinomas, respectively. DNA hypomethylation in urothelial carcinomas significantly correlated with histological grade (p = 0.0012 and 0.0043), invasion depth (p = 0.0055 and 0.0228) and morphological structure (papillary vs nodular, p = 0.0161 and 0.0297) for satellites 2 and 3, respectively. Loss of heterozygosity on at least 1 locus of chromosome 9 was detected in 14 urothelial carcinomas (52%). DNA hypomethylation on satellites 2 (p = 0.0098) and 3 (p = 0.0034) significantly correlated with loss of heterozygosity on chromosome 9.


CONCLUSIONS
DNA hypomethylation on pericentromeric satellite regions may participate in the development and progression of urothelial carcinomas by inducing loss of heterozygosity on chromosome 9.
Nakagawa
Tohru
T
Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Kanai
Yae
Y
Ushijima
Saori
S
Kitamura
Tadaichi
T
Kakizoe
Tadao
T
Hirohashi
Setsuo
S
D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014516:Ureteral Neoplasms / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics; D014571:Urologic Neoplasms / Q000235:genetics*
D004276:DNA, Satellite