胡銳 1 , 田超 1 , 蔣文軍 1 , 魏陽 2 , 姚文秀 2 , 龍啟明 1 , 周行 2 , 王禮陽 2 , 謝華 2
  • 1.四川省腫瘤醫(yī)院乳腺科（四川成都 610041）;;
  • 2.四川省腫瘤醫(yī)院腫瘤內(nèi)科（四川成都 610041）;

目的研究p16基因甲基化在乳腺癌中的分布情況，并探討其與乳腺癌發(fā)生、發(fā)展的關(guān)系。方法采用甲基化特異的PCR技術(shù)檢測四川省腫瘤醫(yī)院乳腺科2008年3～9月期間收治的38例原發(fā)性乳腺癌組織及距離腫瘤＞5 cm以遠(yuǎn)的正常乳腺組織中p16基因啟動子區(qū)CpG島甲基化頻率。結(jié)果乳腺癌組織中p16基因啟動子區(qū)CpG島甲基化頻率〔31.6%（12/38）〕明顯高于其正常乳腺組織〔5.3%（2/38）〕，差異有統(tǒng)計學(xué)意義（P=0.003）。有淋巴結(jié)轉(zhuǎn)移的乳腺癌患者中p16基因甲基化頻率〔45.5%（10/22）〕高于無淋巴結(jié)轉(zhuǎn)移患者〔12.5%（2/16）〕，差異有統(tǒng)計學(xué)意義（P=0.044）。結(jié)論p16基因啟動子區(qū)CpG島甲基化可能在乳腺癌發(fā)生、發(fā)展過程中起著重要作用。

引用本文： 胡銳,田超,蔣文軍,魏陽,姚文秀,龍啟明,周行,王禮陽,謝華. p16基因甲基化在乳腺癌發(fā)展中的作用. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(5): 553-554. doi: 復(fù)制

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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. 楊金巧, 周蕾蕾, 趙俊玲. p16蛋白在乳腺癌中的表達(dá)及其臨床意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 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 基因的純合缺失、高甲基化、突變及其表達(dá) [J]. 中華病理學(xué)雜志, 1999, 28(2): 105108.
  1. 1. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives [J]. Biochim Biophys Acta, 1998, 1378(2): F115F177.
  2. 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. 3. Rocco JW, Sidransky D. p16(MTS1/CDKN2/INK4a) in cancer progression [J]. Exp Cell Res, 2001, 264(1): 4255.
  4. 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. 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. 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. 7. 楊金巧, 周蕾蕾, 趙俊玲. p16蛋白在乳腺癌中的表達(dá)及其臨床意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2000, 7(5): 297298.
  8. 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. 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. 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. 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. 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. 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. 14. 郭山春, 廖松林, 孟振行, 等. 乳腺癌P16 基因的純合缺失、高甲基化、突變及其表達(dá) [J]. 中華病理學(xué)雜志, 1999, 28(2): 105108.