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Detection of RASSF1A aberrant promoter hypermethylation in sputum from chronic smokers and ductal carcinoma in situ from breast cancer patients

Abstract

The newly identified 3p21.3 tumour suppressor gene RASSF1A is methylated in the majority of primary lung tumours, lung tumour cell lines and in a variable percentage of breast tumours. To determine the extent of RASSF1A promoter hypermethylation in early lung tumorigenesis, we analysed sputum samples from lung cancer patients and from current and former smokers using a sensitive methylation-specific PCR (MSP) technique. We also analysed RASSF1A promoter region hypermethylation in trios of normal breast/invasive ductal breast carcinoma/ductal carcinoma in situ (DCIS) from breast cancer patients and DCIS without invasive cancer. We found that 50% of small cell lung cancer (SCLC) and 21% of non-small cell lung cancer (NSCLC) patients had RASSF1A methylation, while one of two former smokers and four of 13 current smokers demonstrated RASSF1A methylation in sputum. Furthermore, two of the four current smokers and one former smoker showing RASSF1A methylation in their sputum developed cancer within 12–14 months of bronchoscopy. In our breast cancer trios, RASSF1A promoter hypermethylation was detected in 65% of invasive cancers, in 42% of corresponding DCIS but in none of the normal breast samples. In addition, we found that three out of 10 DCIS without invasive breast cancer also underwent RASSF1A promoter hypermethylation. Our findings suggest that RASSF1A promoter region hypermethylation may be a useful molecular marker for early detection of lung cancer. Furthermore, since RASSF1A promoter hypermethylation was detected in ductal carcinoma in situ, inactivation of RASSF1A may be an early event in breast tumorigenesis.

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References

  • Agathanggelou A, Honorio S, Macartney DP, Martinez A, Dallol A, Rader R, Fullwood P, Chauhan A, Walker R, Shaw JA, Hosoe S, Lerman MI, Minna JD, Maher ER and Latif F . (2001). Oncogene, 20, 1509–1518.

  • Astuti D, Agathanggelou A, Honorio S, Dallol A, Martinsson T, Kogner P, Cummins C, Neumann HP, Voutilainen R, Dahia P, Eng C, Maher ER and Latif F . (2001). Oncogene, 20, 7573–7577.

  • Belinsky SA, Palmisano WA, Gillil FD, Crooks LA, Divine KK, Winters SA, Grimes MJ, Harms HJ, Tellez CS, Smith TM, Moots PP, Lechner JF, Stidley CA and Crowell RE . (2002). Cancer Res., 62, 2370–2377.

  • Burbee DG, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M and Minna JD . (2001). J. Natl. Cancer Inst., 93, 691–699.

  • Byun DS, Lee MG, Chae KS, Ryu BG and Chi SG . (2001). Cancer Res., 61, 7034–7038.

  • Dammann R, Li C, Yoon JH, Chin PL, Bates S and Pfeifer GP . (2000). Nat. Genet., 25, 315–319.

  • Dammann R, Yang G and Pfeifer GP . (2001). Cancer Res., 61, 3105–3109.

  • Jones PA and Baylin SB . (2002). Nat. Rev. Genet., 3, 415–428.

  • Kersting M, Friedl C, Kraus A, Behn M, Pankow W and Schuermann M . (2000). J. Clin Oncol., 18, 3221–3229.

  • Kuzmin I, Gillespie JW, Protopopov A, Geil L, Dreijerink K, Yang Y, Vocke CD, Duh FM, Zabarovsky E, Minna JD, Rhim JS, Emmert-Buck MR, Linehan WM and Lerman MI . (2002). Cancer Res., 62, 3498–3502.

  • Lee MG, Kim HY, Byun DS, Lee SJ, Lee CH, Kim JI, Chang SG and Chi SG . (2001). Cancer Res., 61, 6688–6692.

  • Lehmann U, Langer F, Feist H, Glockner S, Hasemeier B and Kreipe H . (2002). Am. J. Pathol., 160, 605–612.

  • Lerman and Minna for The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. (2000). Cancer Res., 60, 6116–6133.

  • Lo KW, Kwong J, Hui AB, Chan SY, To KF, Chan AS, Chow LS, Teo PM, Johnson PJ and Huang DP . (2001). Cancer Res., 61, 3877–3881.

  • Morrissey C, Martinez A, Zatyka M, Agathanggelou A, Honorio S, Astuti D, Morgan NV, Moch H, Richards FM, Kishida T, Yao M, Schraml P, Latif F and Maher ER . (2001). Cancer Res., 61, 7277–7281.

  • Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG and Belinsky SA . (2000). Cancer Res., 60, 5954–5958.

  • Viacava P, Naccarato AG and Bevilacqua G . (1999). J. Pathol., 188, 245–251.

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Acknowledgements

This work was supported in part by the Association for International Cancer Research. S Honorio was supported by the Portuguese Foundation for Science & Technology.

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Correspondence to Farida Latif.

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Honorio, S., Agathanggelou, A., Schuermann, M. et al. Detection of RASSF1A aberrant promoter hypermethylation in sputum from chronic smokers and ductal carcinoma in situ from breast cancer patients. Oncogene 22, 147–150 (2003). https://doi.org/10.1038/sj.onc.1206057

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