These results suggest that genotype analysis of the c-Ha-ras-1 locus, in combination with other clinical parameters, may be of prognostic value in assessing the potential for cancer.
Unique and uncommon BamHI allelic restriction fragments of the Ha-ras locus have been reported in the genomes of patients with cancer and of three affected members of a familial melanoma kindred (Krontiris et al., 1986).
A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy.
These data suggest that these genetic alterations are not directly related to Ha-ras expression, and that RFLP of Ha-ras gene is not a useful genetic marker for urothelial cancer.
It was recently reported that different rare alleles at the Ha-ras-1 locus occurred at a significantly higher combined frequency in cancer patients than in an unaffected population.
These deletions seem to be linked with aggressiveness of tumors; a restriction fragment length polymorphism (RFLP) study of c-ha-ras has shown a significant association of the frequency of rare ha-ras alleles in cancer patients compared to that of normal individuals.
Analysis of 426 alleles of the human Ha-ras 1 locus in DNA samples of cancer patients and controls reveals no obvious association between specific restriction fragments and a genetic predisposition to malignancy.
These findings from unmanipulated human neuroblastomas indicate that the Ha-ras gene product (p21) might play a role in the mechanism(s) controlling aggressiveness in this type of tumor in vivo and that the Ha-ras p21 detected by a simple and reproducible immunohistochemical procedure may be of clinical importance in predicting prognosis in patients with this malignancy.
We discuss here the possible role of VTR and allelic deletion of the c-Ha-ras allele in primary human cancers in relation to c-Ha-ras expression, and the usefulness of c-Ha-ras RFLP in the risk assessment of urothelial cancer.
The frequency of unusual alleles was significantly greater in bladder cancer patients and in the combined tumour group than in controls, thus providing support for the association of unique Ha-ras alleles and cancer.
We have assessed the possibility that rare allelic variants of the c-Ha-ras-1 locus may be linked to a susceptibility to malignancy [1]. c-Ha-ras-1 genotypes were scored in 41 patients with myelodysplasia (MDS), 51 patients with acute myeloid leukaemia (AML) and 52 normal subjects.
The occurrence of rare hypervariable Ha-ras alleles or of a rare c-mos allele in white blood cell DNA is claimed to be associated with susceptibility to cancer.
Among the genes located in 11p15, c-Ha-ras 1 (HRAS1), insulin (INS), and insulin-like growth factor II (IGF2) may account for the clinical features and the increased risk for malignancy.
On the contrary, genes of ras family were expressed in more limited numbers of cases except for the Ki-ras gene, which was more frequently expressed by cases of the T-cell immunophenotype with a high malignancy grade.
Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGF beta under anchorage-independent, but not anchorage-dependent, conditions without affecting TGF beta production or receptor characteristics.
Several tumorigenic (benign and malignant) clones have been raised from the human epidermal cell line HaCaT after transfection with the c-Ha-ras oncogene (val 12) (P. Boukamp et al., Cancer Res., 50: 2840-2847, 1990).
With PCR and oligoprobe hybridization, we investigated c-Ha-ras gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non-immunosuppressed patients were also analyzed.
Both the present case-control study (odds ratio, 1.83; 95 percent confidence interval, 1.28 to 2.67; P = 0.002) and the present study combined with our previous study (odds ratio, 2.07; 95 percent confidence interval, 1.47 to 2.92; P < 0.001), as well as the meta-analysis of all 23 studies (odds ratio, 1.93; 95 percent confidence interval, 1.63 to 2.30; chi-square = 57.58; P < 0.001), replicated our original finding and demonstrated a significant association of rare HRAS1 alleles with cancer.