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p16INK4A-alterations in primary angiosarcoma of the liver
A Tannapfel1, M Weihrauch, M Benicke
1Institute of Pathology, University of Leipzig, Germany. tana@medizin.uni-leipzig.de
Background/Aims:
Alterations in the p16 (CDKN2/MTS-1/INK4A) gene have been implicated in the tumorigenesis of different human cancers. Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is the predominant mechanism of p16INK4a gene inactivation in malignant epithelial tumors. This study was performed to determine whether alterations of p16 are involved in the development of angiosarcoma of the liver.
Methods:
The status of p16 was evaluated in 17 angiosarcomas of the liver by methylation-specific PCR (MSP), microsatellite analysis, DNA sequencing and immunohistochemical staining. The results obtained were correlated with histopathological variables and with patient survival.
Results:
Hypermethylation of the 5' CpG island of the p16 gene was found in 12 out of 17 (71%) angiosarcomas examined. Homozygous deletion at the p16 region was present in one case (6%), and loss of heterozygosity was present in two cases (12%). We failed to detect p16 gene missense mutations. The status of p16 correlated with neither histopathological factors nor with the prognosis of the patients with angiosarcomas.
Conclusions:
These data suggest that inactivation of the p16 gene is a frequent event in angiosarcomas of the liver. The most common somatic alteration is promotor methylation of the p16 gene. We failed to establish p16 as independent prognostic factors in these tumors.
Insights
Promoter methylation frequently inactivates the p16 gene in liver angiosarcomas. This study investigated p16 alterations in liver angiosarcoma development and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Alterations in the p16 (CDKN2/MTS-1/INK4A) gene are linked to human cancer development.
- Transcriptional silencing via CpG island hypermethylation is a primary mechanism for p16INK4a gene inactivation in epithelial tumors.
- The role of p16 alterations in liver angiosarcoma pathogenesis requires elucidation.
Purpose of the Study:
- To investigate the involvement of p16 gene alterations in the development of angiosarcoma of the liver.
- To determine the frequency and mechanisms of p16 gene inactivation in liver angiosarcomas.
- To assess the correlation between p16 status and clinicopathological variables or patient survival.
Main Methods:
- Analysis of p16 gene status in 17 liver angiosarcomas using methylation-specific PCR (MSP), microsatellite analysis, DNA sequencing, and immunohistochemical staining.
- Correlation of p16 alterations with histopathological features and patient survival data.
- Evaluation of promoter methylation, gene deletion, and mutation status.
Main Results:
- Hypermethylation of the p16 gene's 5' CpG island was observed in 71% of the examined angiosarcomas.
- Homozygous deletion and loss of heterozygosity at the p16 locus were found in 6% and 12% of cases, respectively.
- No p16 gene missense mutations were detected, and p16 status did not correlate with histopathological factors or prognosis.
Conclusions:
- Inactivation of the p16 gene is a common event in liver angiosarcomas.
- Promoter methylation represents the predominant mechanism of p16 gene alteration in these tumors.
- The p16 gene was not identified as an independent prognostic factor for liver angiosarcoma.