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5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers

Nature Medicine volume 1, pages 686–692 (1995)Cite this article

Abstract

Loss of heterozygosity on chromosome 9p21 is one of the most frequent genetic alterations identified in human cancer. The rate of point mutations of p16, a candidate suppressor gene of this area, is low in most primary tumours with allelic loss of 9p21. Monosomic cell lines with structurally unaltered p16 show methylation of the 5′ CpG island of p16. This distinct methylation pattern was associated with a complete transcriptional block that was reversible upon treatment with 5-deoxyazacytidine. Moreover, de novo methylation of the 5′ CpG island of p16 was also found in approximately 20% of different primary neoplasms, but not in normal tissues, potentially representing a common pathway of tumour suppressor gene inactivation in human cancers.

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Authors and Affiliations

  1. Division of Head and Neck Cancer Research, Department of Otolaryngology, Johns Hopkins School of Medicine, 820 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland, 21205-2195, USA

    Adrian Merlo, Li Mao, Daniel J. Lee & David Sidransky

  2. The Johns Hopkins Oncology Center, 424 N. Bond Street, Baltimore, Maryland, 21231, USA

    James G. Herman, Stephen B. Baylin & David Sidransky

  3. Department of Pathology, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, Maryland, 21287, USA

    Edward Gabrielson & Peter C. Burger

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  1. Adrian Merlo
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  2. James G. Herman
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Merlo, A., Herman, J., Mao, L. et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1, 686–692 (1995). https://doi.org/10.1038/nm0795-686

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