Aberrant DNA methylation of cancer-related genes in giant breast fibroadenoma: a case report

Abstract

IntroductionGiant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, 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 are no previously published data on epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpG islands have confirmed that the aberrant methylation is specific to malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas.Case presentationA 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in her left breast. On physical examination, a 10 × 10 cm lump was detected 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 CpG islands related to cell growth control. We have identified the methylation of five cancer-related CpG islands in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44.ConclusionIn this case report we show for the 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 tumor. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there exist no previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion.

When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer

“…Based on this, specific aberrant DNA methylation patterns have been proposed as predictive and prognostic markers for several cancer types (Okugawa et al 2015 ; D'Errico et al 2020 ; Singh et al 2019 ; Almeida et al 2019 ). Specifically, in breast cancer, previous work of our group has identified that the DNA methylation profiles of tumor suppressor genes correlate with prognosis index (Marzese et al 2010 , 2012 ), with tumor subtypes (Branham et al 2012 ), migration and metastasis capacity (Urrutia et al 2015 ; Marzese et al 2014 ), benign mammary lesions (Marzese et al 2011 ), and, more relevant for the topic of this study, with the laterality of the tumors (Campoy et al 2016 ). In summary, tumor epigenome is influenceable by the microenvironment and can be associated with differential tumor behaviors.…”

Epigenetic Alterations in a Gastric Leiomyoma

“…Hypermethylation at the promoter region of several genes has been shown to be an important mechanism in gene silencing. However, gene-acquired methylation may not necessarily be related with malignant phenotype [ 16 , 17 ]. In this report, we show that a gastric leiomyoma, considered a benign disease, presents methylation in 2–5 of 84 analyzed CpGI, varying in different tumor parts.…”

Identification of Hypermethylation in Hepatocyte Cell Adhesion Molecule Gene Promoter Region in Bladder Carcinoma

“…Some studies have proved that epigenetic changes of multiple TSGs (tumor suppressor genes) were involved in breast pathogenesis 20 . Researchers also demonstrated that aberrant methylated genes played various functions in the cell cycle regulation, proliferation and adhesion 21 . Research of Jelilek J showed that aberrant DNA methylation is associated with CML progression 22 .…”