Regular Article
p16(MTS-1/CDKN2/INK4a) in Cancer Progression

https://doi.org/10.1006/excr.2000.5149Get rights and content

Abstract

Since its discovery as an inhibitor of cyclin-dependent kinases 4 and 6, the tumor suppressor p16 has continued to gain widespread importance in cancer. The high frequency of deletions of p16 in tumor cell lines first suggested an important role for p16 in carcinogenesis. This initial genetic evidence was subsequently strengthened by numerous studies documenting p16 inactivation in kindreds with familial melanoma. Moreover, a high frequency of p16 gene alterations was found in primary tumors, while recent studies have identified p16 promoter methylation as a major mechanism of tumor-suppressor-gene silencing. Additional insight into p16's role in cancer has come from the genetic analysis of precancerous lesions and various tissue culture models. It is now believed that loss of p16 is an early and often critical event in tumor progression. Consequently, p16 is a major tumor-suppressor gene whose frequent loss occurs early in many human cancers.

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      CDKN2A alterations that can affect p16 expression include promoter hyper-methylation, coding mutations, and deletions. These alterations have been shown in a wide range of cancers including pancreatic adenocarcinoma, melanoma, lymphomas, esophageal squamous cell carcinomas, gastric and colorectal cancers.25,26 Our data highlight the pitfalls present when utilizing p16 staining outside of the head and neck given the diversity of neoplasms that can express p16.

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    To whom correspondence and reprint requests should be addressed at the Department of Otolaryngology, Johns Hopkins University, 720 Rutland Avenue, Ross 818, Baltimore, MD 21205.

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