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ras oncogene activation in human ovarian carcinoma
L J van 't Veer1, R Hermens, L A van den Berg-Bakker
1Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
Oncogene
|February 1, 1988
Summary
This study found c-K-ras2 gene amplification in three human ovarian tumors, with increased mRNA and protein levels. No ras mutations were detected, and amplification did not correlate with tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Proto-oncogene amplification and ras mutations are implicated in tumorigenesis.
- Ovarian cancer is a significant health concern with complex genetic underpinnings.
Purpose of the Study:
- To investigate the prevalence of proto-oncogene amplification and ras mutations in human ovarian tumors.
- To assess the correlation between ras gene alterations and ovarian tumor characteristics.
Main Methods:
- Screening of 37 fresh human ovarian tumor biopsies for gene amplification and point mutations.
- Quantitative assessment of c-K-ras2 amplification using dilution experiments and soft laser densitometry.
- Analysis of c-K-ras2 mRNA and p21 ras protein levels via RT-PCR and Western blotting.
- Detection of point mutations in Harvey-, Kirsten-, and N-ras oncogenes using polymerase chain reaction (PCR).
Main Results:
- c-K-ras2 gene amplification was detected in three out of 37 ovarian tumor samples.
- Elevated levels of c-K-ras2 mRNA and p21 ras protein were observed in tumors with amplification.
- No point mutations in codons 12 or 61 of Harvey-, Kirsten-, or N-ras were found.
- No correlation was established between ras activation (amplification or mutation) and tumor progression or histological subtype.
- DNA from one amplified tumor exhibited high transforming activity in NIH 3T3 assays, but c-K-ras2 was not the transforming gene.
Conclusions:
- c-K-ras2 amplification occurs in a subset of human ovarian tumors and leads to increased gene product expression.
- Ras mutations are not a common mechanism of ras activation in this cohort of ovarian cancers.
- The role of c-K-ras2 amplification in ovarian tumorigenesis requires further investigation, especially given the observed transforming activity independent of c-K-ras2.