High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma

Andre L. Reed, Joseph Califano, Paul Cairns, William H. Westra, Richard M. Jones, Wayne Martin Koch, Steven Ahrendt, Yolanda Eby, Duane Sewell, Homaira Nawroz, Jiri Bartek, David Sidransky

Research output: Contribution to journalArticle

Abstract

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50, p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83%) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67%) harbored homozygous deletions, 5 (21%) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.

Original languageEnglish (US)
Pages (from-to)3630-3633
Number of pages4
JournalCancer Research
Volume56
Issue number16
StatePublished - Aug 15 1996

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p16 Genes
Tumor Suppressor Genes
Methylation
Immunohistochemistry
Staining and Labeling
Frameshift Mutation
CpG Islands
Sequence Deletion
Gene Silencing
Southern Blotting
Point Mutation
Microsatellite Repeats
Sequence Analysis
Exons
Neoplasms
Monoclonal Antibodies
Carcinoma, squamous cell of head and neck

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Reed, A. L., Califano, J., Cairns, P., Westra, W. H., Jones, R. M., Koch, W. M., ... Sidransky, D. (1996). High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Research, 56(16), 3630-3633.

High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. / Reed, Andre L.; Califano, Joseph; Cairns, Paul; Westra, William H.; Jones, Richard M.; Koch, Wayne Martin; Ahrendt, Steven; Eby, Yolanda; Sewell, Duane; Nawroz, Homaira; Bartek, Jiri; Sidransky, David.

In: Cancer Research, Vol. 56, No. 16, 15.08.1996, p. 3630-3633.

Research output: Contribution to journalArticle

Reed, AL, Califano, J, Cairns, P, Westra, WH, Jones, RM, Koch, WM, Ahrendt, S, Eby, Y, Sewell, D, Nawroz, H, Bartek, J & Sidransky, D 1996, 'High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma', Cancer Research, vol. 56, no. 16, pp. 3630-3633.
Reed AL, Califano J, Cairns P, Westra WH, Jones RM, Koch WM et al. High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Research. 1996 Aug 15;56(16):3630-3633.
Reed, Andre L. ; Califano, Joseph ; Cairns, Paul ; Westra, William H. ; Jones, Richard M. ; Koch, Wayne Martin ; Ahrendt, Steven ; Eby, Yolanda ; Sewell, Duane ; Nawroz, Homaira ; Bartek, Jiri ; Sidransky, David. / High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. In: Cancer Research. 1996 ; Vol. 56, No. 16. pp. 3630-3633.
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abstract = "The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50, p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83{\%}) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67{\%}) harbored homozygous deletions, 5 (21{\%}) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.",
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AU - Cairns, Paul

AU - Westra, William H.

AU - Jones, Richard M.

AU - Koch, Wayne Martin

AU - Ahrendt, Steven

AU - Eby, Yolanda

AU - Sewell, Duane

AU - Nawroz, Homaira

AU - Bartek, Jiri

AU - Sidransky, David

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