Study of allelic losses on 3p, 6q, and 17p in human urothelial cancer.

Forty-eight transitional cell carcinomas of the bladder and three transitional cell carcinomas of the renal pelvis were examined for loss of heterozygosity (LOH) on chromosomes 3p, 6q, and 17p. The most frequent allelic loss was seen on 17p (18/36, 50%) followed by 6q (6/22, 27%), and 3p (5/22, 23%). In cases with LOH at more than one locus, the same DNA sample often varied in degree of signal reduction for missing alleles. This observation indicates that LOH studies can serve to detect intratumor heterogeneity. No correlation was found between allelic losses at these chromosome arms and tumor grade and stage. Allelic losses on 6q were associated with tumors having a solid growth pattern; in this kind of tumors, allelic losses on 3p were associated with invasion.

Restriction fragment length polymorphism of the L-myc gene is not a prognostic factor in bladder cancer patients.

The L-myc restriction fragment length polymorphism has been suggested to be of prognostic significance in some types of primary tumours. We examined the prognostic and susceptibility significance of the L-myc genotype in a group of 98 bladder cancer patients. The L-myc genotype did not correlate with any pathologic parameter and does not offer any clinical utility in patients with bladder cancer.

Analysis of 3p allelic losses in renal cell carcinomas: comparison with cytogenetic results.

We performed a study of loss of heterozygosity (LOH) at 3p by restriction fragment length polymorphism analysis in a series of 22 renal tumors. In 11 cases, molecular results could be compared with those of cytogenetic studies. The highest frequency of allelic losses at 3p was seen in clear cell non-papillary renal tumors, whereas none of the papillary renal cell carcinomas showed LOH at 3p. Allelic losses on 3p were found to be independent of tumor grade or stage or both. One case analyzed showed a discrepancy between cytogenetic and LOH studies. This tumor displayed rearrangements of chromosome 3 and no LOH at the c-RAF-1 (close to the Von Hippel Lindau gene) locus.

[Low incidence of mutations in codon 12 of the c-K-ras gene in bladder cancer]. / Baja incidencia de mutación del codon 12 del gen c-K-ras en el cáncer vesical.

During vesical carcinogenesis a variety of genetic alterations such as oncogene mutation or loss of suppressor genes have been detected. Codon 12 mutation of the c-K-ras gene has been seen with a high frequency in several human neoplasias but its participation in the development of vesical cancers has not been fully dilucidated. Using the DNA restriction fragments polymorphism (RFLP) technique enhanced by a polymerase chain reaction (PCR) a study has been made of codon 12 mutation at the c-K-ras gene in 55 patient with vesical cancer undergoing surgery between 1991 and 1992. The tumoral stage was superficial (Ta-Tl) in 24 cases, infiltrant (T2-T4) in 28 cases and unknown in 3 cases. Two patients (3.6%) showed codon 12 mutation at the c-K-ras gene. One case was a fast evolving infiltrant tumour (T2-T3) which caused death of the patient after 4 months while the other case was a surface tumour (G2Ta) which relapsed early, the pathological anatomy revealing a stage T2-T3 squamous carcinoma. Our results suggest that codon 12 mutation at the c-K-ras gene is not a meaningful genetic change in the genesis of vesical cancer. Its emergence, however, appears to be related to a more aggressive tumoural behaviour.