ArticleThe American journal of pathology1998
CDKN2A gene deletions and loss of p16 expression occur in osteosarcomas that lack RB alterations.
Article in The American journal of pathology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 111 citations in OpenAlex.
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- Genomic and transcriptomic comparison of post-radiation versus sporadic sarcomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Establishment of a novel cellular model for myxofibrosarcoma heterogeneity.Scientific reports · 2017Article
- Review of Osteosarcoma and Current Management.Rheumatology and therapy · 2016Review
- Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.Carcinogenesis · 2015Review
- Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.Carcinogenesis · 2015Review
- Genomic heterogeneity of osteosarcoma - shift from single candidates to functional modules.PloS one · 2015Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcomas often suffer mutations of the RB (retinoblastoma) gene, with resultant inactivation of the pRb protein. pRb is one component in a cell-cycle control pathway that includes the p16 (encoded by the CDKN2A gene) and cyclin-dependent kinase 4 (cdk4, encoded by the CDK4 gene) proteins. We therefore sought to determine whether the CDKN2A and CDK4 genes were altered in those osteosarcomas that lacked RB inactivation. Twenty-one osteosarcomas (2 low-grade and 19 high-grade) were evaluated for homozygous deletion of the CDKN2A gene, CDK4 amplification, and allelic loss of the RB gene, as well as for expression of p16 and pRb proteins. Five high-grade osteosarcomas showed loss of p16 expression; four of these had homozygous CDKN2A deletions, and the fifth had a probable deletion obscured by numerous nonneoplastic, p16-immunopositive multinucleated giant cells. Thus, p16 immunohistochemistry may provide a sensitive means for assessing CDKN2A status. Twelve tumors (including the two low-grade osteosarcomas) were immunopositive for pRb, and nine tumors were immunonegative for pRb. Of the five cases with CDKN2A/p16 alterations, none had allelic loss of the RB gene and all expressed pRb, suggesting that each of these tumors had an intact RB gene. None of the tumors showed CDK4 amplification. No alterations were detected in the two low-grade osteosarcomas. This study suggests that CDKN2A is a tumor suppressor inactivated in osteosarcomas that lack RB mutations and that the p16-pRb cell-cycle control pathway is deregulated in a large number of high-grade osteosarcomas.
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