Skip to main content

Advertisement

Log in

Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Purpose

The link between BRCA1 dysfunction and basal-like breast cancer or triple-negative breast cancer (TNBC) has been suggested; however, the associations of other factors involved in the Fanconi anemia (FA)/BRCA pathway with the pathogenesis of basal-like breast cancer remain unidentified. FANCF protein is a component of the FA core complex. The methylation of CpG islands in the FANCF gene plays an important role in occurrence of ovarian cancer and also is an important regulator of cisplatin sensitivity of ovarian cancer. The purpose of this study is to investigate the frequency of FANCF methylation, and to discuss its involvement in the pathogenesis of TNBC and its potency as a predictor of cisplatin sensitivity for breast cancer.

Methods

The methylation of the FANCF gene promoter was investigated, using methylation-specific PCR, in genomic DNA of 99 invasive breast carcinoma specimens obtained from Japanese patients.

Results

FANCF methylation was recognized in only 4 of 99 cases (4.0%). No significant correlation was found between FANCF methylation and the expression of ER, PR, HER2, and TNBC.

Conclusions

FANCF methylation is a rare event in Japanese primary invasive breast cancer. This suggests it is not involved in the pathogenesis of TNBC, and it could not be used as a predictor of cisplatin sensitivity in breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.

    Article  PubMed  Google Scholar 

  2. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.

    Article  PubMed  CAS  Google Scholar 

  3. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.

    Article  PubMed  CAS  Google Scholar 

  4. Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer. 2004;4:814–9.

    Article  PubMed  CAS  Google Scholar 

  5. Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006;25:5846–53.

    Article  PubMed  CAS  Google Scholar 

  6. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.

    Article  PubMed  CAS  Google Scholar 

  7. Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81.

    Article  PubMed  Google Scholar 

  8. Lyakhovich A, Surralles J. Disruption of the Fanconi anemia/BRCA pathway in sporadic cancer. Cancer Lett. 2006;232:99–106.

    Article  PubMed  CAS  Google Scholar 

  9. Wang W. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet. 2007;8:735–48.

    Article  PubMed  CAS  Google Scholar 

  10. Joenje H, Patel KJ. The emerging genetic and molecular basis of Fanconi anaemia. Nat Rev Genet. 2001;2:446–57.

    Article  PubMed  CAS  Google Scholar 

  11. de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, et al. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet. 2000;9:2665–74.

    Article  PubMed  Google Scholar 

  12. Wang Z, Li M, Lu S, Zhang Y, Wang H. Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway. Cancer Biol Ther. 2006;5:256–60.

    Article  PubMed  CAS  Google Scholar 

  13. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med. 2003;9:568–74.

    Article  PubMed  CAS  Google Scholar 

  14. Marsit CJ, Liu M, Nelson HH, Posner M, Suzuki M, Kelsey KT. Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival. Oncogene. 2004;23:1000–4.

    Article  PubMed  CAS  Google Scholar 

  15. Meyer S, White DJ, Will AM, Eden T, Sim A, Brown R, et al. No evidence of significant silencing of Fanconi genes FANCF and FANCB or Nijmegen breakage syndrome gene NBS1 by DNA hyper-methylation in sporadic childhood leukaemia. Br J Haematol. 2006;134:61–3.

    Article  PubMed  CAS  Google Scholar 

  16. Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, et al. Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Cancer Res. 2004;64:2994–7.

    Article  PubMed  CAS  Google Scholar 

  17. Neveling K, Kalb R, Florl AR, Herterich S, Friedl R, Hoehn H, et al. Disruption of the FA/BRCA pathway in bladder cancer. Cytogenet Genome Res. 2007;118:166–76.

    Article  PubMed  CAS  Google Scholar 

  18. Wei M, Xu J, Dignam J, Nanda R, Sveen L, Fackenthal J, et al. Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers. Breast Cancer Res Treat. 2008;111:113–20.

    Article  PubMed  CAS  Google Scholar 

  19. Lim SL, Smith P, Syed N, Coens C, Wong H, van der Burg M, et al. Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer. Br J Cancer. 2008;98:1452–6.

    Article  PubMed  CAS  Google Scholar 

  20. Olopade OI, Wei M. FANCF methylation contributes to chemoselectivity in ovarian cancer. Cancer Cell. 2003;3:417–20.

    Article  PubMed  CAS  Google Scholar 

  21. Kimura K, Toyooka S, Tsukuda K, Yamamoto H, Suehisa H, Soh J, et al. The aberrant promoter methylation of BMP3b and BMP6 in malignant pleural mesotheliomas. Oncol Rep. 2008;20:1265–8.

    PubMed  CAS  Google Scholar 

  22. Hunter F, Xie J, Trimble C, Bur M, Li KC. Rhodamine-RCA in vivo labeling guided laser capture microdissection of cancer functional angiogenic vessels in a murine squamous cell carcinoma mouse model. Mol Cancer. 2006;5:5.

    Article  PubMed  Google Scholar 

  23. Sun J, Chen Z, Zhu T, Yu J, Ma K, Zhang H, et al. Hypermethylated SFRP1, but none of other nine genes “informative” for western countries, is valuable for bladder cancer detection in mainland China. J Cancer Res Clin Oncol. 2009 (in press).

  24. Tokunaga E, Kimura Y, Oki E, Ueda N, Futatsugi M, Mashino K, et al. Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer. 2006;118:284–9.

    Article  PubMed  CAS  Google Scholar 

  25. Tokunaga E, Oki E, Nishida K, Koga T, Yoshida R, Ikeda K, et al. Aberrant hypermethylation of the promoter region of the CHFR gene is rare in primary breast cancer. Breast Cancer Res Treat. 2006;97:199–203.

    Article  PubMed  CAS  Google Scholar 

  26. Dhillon VS, Shahid M, Husain SA. CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. Mol Cancer. 2004;3:33.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Ms T. Shishino and Ms K. Yamashita for their valuable technical assistance. This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eriko Tokunaga.

About this article

Cite this article

Tokunaga, E., Okada, S., Kitao, H. et al. Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer. Breast Cancer 18, 120–123 (2011). https://doi.org/10.1007/s12282-009-0175-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-009-0175-z

Keywords

Navigation