Hum Pathol  1992 Nov;23(11):1199-204 

Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in
urinary bladder carcinomas.

Czerniak B, Cohen GL, Etkind P, Deitch D, Simmons H, Herz F, Koss LG.

Department of Pathology, Montefiore Medical Center, Albert Einstein College of
Medicine, Bronx, NY 10467.

This report concerns the study of Ha-ras gene mutations and ras p21 expression
in primary tumors of the urinary bladder. Polymerase chain reaction-based
techniques and computerized image analysis were used. The data obtained were
related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T)
at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was
greater in grade III (65%) than in grade II (44%) tumors; no mutations were
observed in grade I tumors. The mutation was observed more often in aneuploid
(58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen
and no codon 61 mutation was detected. The tumors were also tested for the A-->G
mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D
mutations were identified in seven high-grade aneuploid tumors; six were
invasive. The levels of the ras gene product p21 were approximately 10 times
higher in tumors with intron D mutation than in those without. These findings
confirm on human bladder tumors the observations of the effect of synchronous
exon-intron mutations reported on the bladder cancer cell line T24. Our results
are the first demonstration of Ha-ras intron D alterations in human tumor
tissues and suggest that concurrent mutations at codon 12 and intron D of this
gene within the same tumor may contribute to the aggressive behavior of human
bladder carcinomas.

PMID: 1427748 [PubMed - indexed for MEDLINE]