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Ras oncogenes and p53 tumor suppressor gene analysis in cardiac myxomas
H Karga1, P Papaioannou, M Karayianni
1Endocrine Unit, Alexandra Hospital, Athens, Greece.
Abstract:
Although ras oncogenes and p53 tumor suppressor gene mutations are implicated in the development of several human tumors, little is known about their role in the pathogenesis of primary cardiac tumors. Paraffin-embedded tissue from 19 cardiac myxomas were investigated for the presence of ras oncogenes and p53 tumor suppressor gene abnormalities. Immunohistochemical analysis was used to identify the accumulation of p21-ras and p53 proteins. A polymerase chain reaction was used to amplify exons 1 and 2 of the ras genes and exons 5 to 8 of the p53 gene. The PCR products were analyzed by single strand conformation polymorphism analysis and by direct DNA sequencing. Three of 19 myxomas showed strong positive staining for the ras p21 protein. In contrast, nuclear p53 was not detectable in any of the myxomas. Among the ras p21 immunopositive myxomas, 2 were heterozygous for a missense point mutation of the K-ras, Gly 12Asp. Further screening of the remaining myxomas showed no mutation or even silent polymorphism in any exon of the ras and p53. The results suggest that although genetic alterations of ras oncogenes and p53 are uncommon events in cardiac myxomas, ras mutations may be involved in the pathogenesis of a subgroup of this type of tumor.
Insights
Ras oncogene mutations, not p53, were found in some cardiac myxomas. These ras gene alterations suggest a potential role in the development of a subset of these primary heart tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cardiovascular Pathology
Background:
- Ras oncogenes and p53 tumor suppressor genes are crucial in many human cancers.
- Their specific roles in primary cardiac tumors, like myxomas, are not well understood.
Purpose of the Study:
- To investigate the presence and significance of ras oncogene and p53 tumor suppressor gene abnormalities in cardiac myxomas.
- To determine if these genetic alterations contribute to the pathogenesis of cardiac myxomas.
Main Methods:
- Immunohistochemistry was used to detect p21-ras and p53 protein accumulation in 19 cardiac myxoma tissues.
- Polymerase chain reaction (PCR) amplified specific ras and p53 gene exons.
- Single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing identified genetic mutations.
Main Results:
- Three out of 19 myxomas showed positive staining for the p21-ras protein.
- No detectable nuclear p53 protein was found in any myxoma samples.
- Two of the ras p21-positive myxomas had a heterozygous missense point mutation in the K-ras gene (Gly12Asp).
- No other ras or p53 mutations or polymorphisms were detected in the remaining samples.
Conclusions:
- Genetic alterations in ras oncogenes and p53 are infrequent in cardiac myxomas.
- Ras gene mutations may play a role in the development of a specific subset of cardiac myxomas.
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