Abstract Background: Recently, the p16/CDKN2/MTS1 gene in the 9p21-22 region has been offered as a candidate tumor suppressor gene. We examined the frequency of hemizygous and homozygous deletions of p16/CDKN2 in head and neck squamous cell carcinoma (HNSCC) using a quantitative polymerase chain reaction (PCR) method. Design: Twenty-one HNSCC and 12 corresponding normal DNA samples were examined for deletion of p16/CDKN2 using PCR amplification and fluorescent quantification of DNA. All tumor and normal DNA samples were also amplified with fluorescein-labeled primers for a control DNA marker on chromosome 8p (D8S265). The ratios of the observed fluorescence of the p16/CDKN2 and 8p PCR products were compared. Setting and participants: Patients with HNSCC scheduled to undergo surgical resection of their tumors were recruited. After the specimen was removed, a portion of the tissue was snap frozen for further DNA extraction. Results: Eight tumors (38%) had p16/CDKN2-D8S265 ratios of greater than 0.75; 8 tumors (38%), from 0.25 to 0.75; and 5 tumors (24%), of less than 0.25, the average ratio in this last group being 0.06. Conclusions: These ratios suggest a higher rate of homozygous deletion than previously reported and significant probable hemizygous deletion of the p16/CDKN2 gene in HNSCC.Arch Otolaryngol Head Neck Surg. 1997;123:863-867 References 1. Parkin D, Laara F, Muir C. Cancer incidence in five continents: comparability and quality of data . Int J Cancer . 1988;41:184-197.Crossref 2. Kamb A. Cell cycle regulators and cancer . Trends Genet . 1995;11:136-140.Crossref 3. Van der Riet P. Nawroz H, Hruban RH, et al. Frequent loss of chromosome 9p21 -22 early in head and neck cancer progression . Cancer Res . 1994;54:1156-1158. 4. Serrano M, Hannon GJ, Beach D, et al. A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4 . Nature . 1993;366:704-707.Crossref 5. Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types . Science . 1994;264:436-439.Crossref 6. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of cyclindependent kinase-4 inhibitor gene in multiple human cancers . Nature . 1994;368: 753-756.Crossref 7. Mori T, Miura K, Aoki T, Mishihira T, Mori S, Nakamura Y. Frequent somatic mutations of the MTS1/CDK4I gene in esophageal cancer . Cancer Res . 1994;54: 3396-3397. 8. Zhang SY, Klein-Szanto AJ, Sauter ER, Shafarenko M, Mitsunaga S, Nobori T. Higher frequency of alterations in the p16/CDKN1 gene squamous carcinoma lines than in primary tumors of the head and neck . Cancer Res . 1994;54:5050-5053. 9. Srivatsan E, Benedict W, Stanbridge E. Implications of chromosome 11 in suppression of neoplastic expression in human cell hybrids . Cancer Res . 1986;46: 6174-6179. 10. Weissenbach J, Gyapay G, Dib C, et al. A second generation linkage map . Nature . 1992;359:794-801.Crossref 11. Van Dyke DL, Worsham MJ, Benninger MS, Krause CJ, Baker SR, Wolf GT. Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region . Genes Chromosomes Cancer . 1994;9:192-206.Crossref 12. Nawroz H, van der Riet P, Hruban RH, Koch W, Ruppert JM, Sidransky D. Allelotype of head and neck squamous carcinoma . Cancer Res . 1994;54:1152-1155. 13. Reed AL, Califano J. Cairns P, et al. High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma . Cancer Res . 1996; 56:3630-3633. 14. Cairns P, Mao L, Merlo A, et al. Rates of p16 (MTS1) mutations in primary tumors with 9p loss . Science . 194;265:415-417.Crossref
Archives of Otolaryngology - Head & Neck Surgery – American Medical Association
Published: Aug 1, 1997
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