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Alterations of the p16INK4A gene in human ovarian cancers
1Department of Reproductive Physiology and Endocrinology, Kyushu University, Beppu, Japan.
Abstract:
The p16INK4A gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene. We examined p16 gene alterations in 30 primary ovarian cancers and 11 ovarian cancer cell lines. Five of the primary cancers (16.7%) had lost both p16INK4A genes. In addition, four cancers (13.3%) contained five kinds of missense mutations and a one-base deletion. Three cell lines had homozygous deletions of p16 genes, and one cell line had multiple intragenic mutations. There was also suppressed transcription of the p16 gene in one cell line. Some point mutations occurred in the conserved ankylin consensus region. These observations suggest that p16 is a functional target for ovarian carcinogenesis and that p16 alterations occurred in the primary cancers.
Insights
Alterations in the p16INK4A gene, a tumor suppressor, were found in ovarian cancers. These genetic changes, including deletions and mutations, suggest p16INK4A is a target in ovarian carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p16INK4A gene encodes a protein that regulates the cell cycle.
- p16INK4A is considered a potential tumor-suppressor gene.
- Ovarian cancer is a significant health concern with complex genetic underpinnings.
Purpose of the Study:
- To investigate alterations of the p16INK4A gene in primary ovarian cancers and cell lines.
- To determine if p16INK4A gene mutations and deletions are associated with ovarian carcinogenesis.
- To assess the functional impact of observed p16INK4A alterations.
Main Methods:
- Analysis of p16INK4A gene status (deletions, mutations) in 30 primary ovarian cancers.
- Examination of p16INK4A gene alterations in 11 ovarian cancer cell lines.
- Assessment of p16INK4A gene transcription levels in cell lines.
Main Results:
- Loss of both p16INK4A genes was observed in 16.7% of primary ovarian cancers.
- Missense mutations and a one-base deletion in p16INK4A were found in 13.3% of primary cancers.
- Homozygous deletions and intragenic mutations of p16INK4A were detected in cell lines, along with suppressed transcription.
Conclusions:
- p16INK4A alterations, including genetic and transcriptional changes, are frequent in ovarian cancer.
- These findings support p16INK4A as a functional target in ovarian carcinogenesis.
- The observed alterations suggest a role for p16INK4A in the development of primary ovarian cancers.