Role of Methylation of p16 Gene in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

胡锐 ¹ , 田超 ¹ , 蒋文军 ¹ , 魏阳 ² , 姚文秀 ² , 龙启明 ¹ , 周行 ² , 王礼阳 ² , 谢华 ²

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Keywords：

乳腺癌; p16基因; 甲基化

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目的研究p16基因甲基化在乳腺癌中的分布情况，并探讨其与乳腺癌发生、发展的关系。方法采用甲基化特异的PCR技术检测四川省肿瘤医院乳腺科2008年3～9月期间收治的38例原发性乳腺癌组织及距离肿瘤＞5 cm以远的正常乳腺组织中p16基因启动子区CpG岛甲基化频率。结果乳腺癌组织中p16基因启动子区CpG岛甲基化频率〔31.6%（12/38）〕明显高于其正常乳腺组织〔5.3%（2/38）〕，差异有统计学意义（P=0.003）。有淋巴结转移的乳腺癌患者中p16基因甲基化频率〔45.5%（10/22）〕高于无淋巴结转移患者〔12.5%（2/16）〕，差异有统计学意义（P=0.044）。结论p16基因启动子区CpG岛甲基化可能在乳腺癌发生、发展过程中起着重要作用。

Citation： 胡锐,田超,蒋文军,魏阳,姚文秀,龙启明,周行,王礼阳,谢华. Role of Methylation of p16 Gene in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(5): 553-554. doi: Copy

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11.	DeInnocentes P, Agarwal P, Bird RC. Phenotyperescue of cyclindependent kinase inhibitor p16/INK4A defects in a spontaneous canine cell model of breast cancer [J]. J Cell Biochem, 2009,106(3): 491505.
12.	Vallian S, Sedaghat M, Nassiri I, et al. Methylation status of p16 INK4A tumor suppressor gene in Iranian patients with sporadic breast cancer [J]. J Cancer Res Clin Oncol, 2009, 135(8): 991996.
13.	Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers [J].Cancer Res, 1995, 55(20): 45254530.
14.	郭山春, 廖松林, 孟振行, 等. 乳腺癌P16 基因的纯合缺失、高甲基化、突变及其表达 [J]. 中华病理学杂志, 1999, 28(2): 105108.

1. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives [J]. Biochim Biophys Acta, 1998, 1378(2): F115F177.
2. Liggett WH Jr, Sidransky D. Role of the p16 tumor suppressor gene in cancer [J]. J Clin Oncol, 1998, 16(3): 11971206.
3. Rocco JW, Sidransky D. p16(MTS1/CDKN2/INK4a) in cancer progression [J]. Exp Cell Res, 2001, 264(1): 4255.
4. Merlo A, Herman JG, Mao L, et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers [J]. Nat Med, 1995, 1(7): 686692.
5. Zhao Y, Zhang S, Fu B, et al. Abnormalities of tumor suppressor genes P16 and P15 in primary maxillofacial squamous cell carcinomas [J]. Cancer Genet Cytogenet, 1999, 112(1): 2633.
6. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cellcycle control causing specific inhibition of cyclin D/CDK4 [J]. Nature, 1993, 366(6456): 704707.
7. 杨金巧, 周蕾蕾, 赵俊玲. p16蛋白在乳腺癌中的表达及其临床意义 [J]. 中国普外基础与临床杂志, 2000, 7(5): 297298.
8. Bohn OL, FuertesCamilo M, Navarro L, et al. p16INK4a expression in basallike breast carcinoma [J]. Int J Clin Exp Pathol, 2010, 3(6): 600607.
9. Hinshelwood RA, Melki JR, Huschtscha LI, et al. Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning [J]. Hum Mol Genet, 2009, 18(16): 30983109.
10. Witcher M, Emerson BM. Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary [J]. Mol Cell, 2009, 34(3): 271284.
11. DeInnocentes P, Agarwal P, Bird RC. Phenotyperescue of cyclindependent kinase inhibitor p16/INK4A defects in a spontaneous canine cell model of breast cancer [J]. J Cell Biochem, 2009,106(3): 491505.
12. Vallian S, Sedaghat M, Nassiri I, et al. Methylation status of p16 INK4A tumor suppressor gene in Iranian patients with sporadic breast cancer [J]. J Cancer Res Clin Oncol, 2009, 135(8): 991996.
13. Herman JG, Merlo A, Mao L, et al. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers [J].Cancer Res, 1995, 55(20): 45254530.
14. 郭山春, 廖松林, 孟振行, 等. 乳腺癌P16 基因的纯合缺失、高甲基化、突变及其表达 [J]. 中华病理学杂志, 1999, 28(2): 105108.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of Methylation of p16 Gene in Breast Cancer

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