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A Novel p16^INK4A Transcript¹

Department of Otolaryngology—Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196 [L. M., A. M., G. B., D. S.], and Department of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 [G. I. S., C. D. E., B. J. R.]

p16^INK4A and p15^INK4B were initially identified as potent inhibitors of activated cyclin/cyclin-dependent kinase complexes. These genes were colocalized to chromosome 9p21, and p16 was subsequently found to be mutated in familial melanoma and deleted in a wide variety of sporadic cancers. We recently found that de novo methylation of a 5' CpG island led to transcriptional block of full-length p16 in many neoplasms. However, the presence of a truncated p16 transcript in methylated cell lines led us to investigate the presence of an alternative promoter or initiation site. We have now identified an abundant alternative p16 transcript in both methylated and unmethylated cell lines generated from a novel sequence (exon 1ß) potentially involved in the complex regulation of these critical cell cycle genes.

¹ Supported by Lung Spore Grant CA-58184-01, a Collaborative Research Agreement with Oncor, Inc. (Gaithersburg, MD), and CA94550 sponsored by the U.S. Department of Energy. Oncor, Inc. provided research funding for the study described in this paper. Under an agreement between Oncor and the Johns Hopkins University, Dr. Sidransky is entitled to a share of sales royalty received by the University from Oncor. Under that agreement, the University and Dr. Sidransky also have received Oncor stock which, under University policy, cannot be traded until 2 years after the first commercial sales of the products related to this research. Dr. Sidransky also serves as a member of the Scientific Advisory Board of OncorMed, Inc., an Oncor subsidiary, which is commercializing some of Oncor's technology. The terms of this arrangement have been reviewed and approved by the University in accordance with its conflict of interest policies.

² To whom requests for reprints should be addressed, at Department of Otolaryngology—Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196.

Received 5/ 5/95. Accepted 6/ 2/95.

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