CONICET | Buscador de Institutos y Recursos Humanos

Abstract Introduction: Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands (CpGIs) in promoter regions is known to be involved in silencing of genes (e.g., tumor-suppressor genes) and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non giant breast fibroadenoma. In this particular case, there is no previously published data of epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpGIs, have confirmed that the aberrant methylation is specific of malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas. Case presentation: A 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in the left breast. At physical examination, a 10x10-cm lump was noted and axillary lymph nodes were not enlarged. After surgical removal the lump was diagnosed as a giant fibroadenoma. Because of the high growth rate of this benign tumor, we decided to analyze the methylation status of 49 CpGIs related to cell growth control. We have identified the methylation of five cancer-related CpGIs in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44. Conclusion: In this report we show for first time the methylation analysis of a giant fibroadenoma. The detection of methylation of these five cancer-related regions indicates substantial epigenomic differences with non-giant fibroadenomas. Epigenetic alterations could explain the higher growth rate of this disease. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there existed non previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion.