BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls

Bosviel, Rémy; Garcia, Stéphane; Lavediaux, Guillaume; Michard, Emilie; Dravers, Marine; Kwiatkowski, Fabrice; Bignon, Yves‐Jean; Bernard‐Gallon, Dominique

doi:10.1016/j.canep.2012.02.001

Cited by 54 publications

(54 citation statements)

References 26 publications

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“…Previous studies have tested average TS promoter methylation in blood as a biomarker for BC risk 10, 11, 12. However, average methylation of millions of DNA molecules in a genomic DNA sample is a surrogate marker which is sometimes difficult to interpret.…”

mentioning

confidence: 99%

Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients

Böck

Appenzeller

Haertle

et al. 2018

Intl Journal of Cancer

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To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2‐mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age‐matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%). With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%), there was no significant difference between patients and controls. One of 36 HR BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent with a disease‐causing epimutation. Approximately one third (15 of 44) EO BC patients exhibited increased rates of single CpG methylation errors in multiple TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS genes. We propose that epigenetic abnormalities in normal body cells are indicative of disturbed mechanisms for maintaining low methylation and appropriate expression levels and may be associated with an increased BC risk.

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mentioning

confidence: 99%

Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients

Böck

Appenzeller

Haertle

et al. 2018

Intl Journal of Cancer

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show abstract

“…The role of epigenetic processes in breast cancer has been widely reported (Bediaga et al 2010, Huang et al 2011; Table 1). Methylation of the BRCA1 gene promoter has been described in sporadic breast tumors and has also been suggested as a prognosis factor as it is more frequent in the invasive forms of breast cancer (Bosviel et al 2012). A relationship between BRCA1 hypermethylation and tumor stage was also described in ovarian cancer, the gene being hypermethylated in stages II and III when compared with stage I, which supports the idea that loss of BRCA1 expression is correlated with a more advanced stage of ovarian cancer and suggests the potential of this gene as a biomarker for ovarian and breast cancers.…”

Section: Sporadic Endocrine Diseasesmentioning

confidence: 99%

“…TIMP3, which is thought to suppress primary tumor growth, is also downregulated in prostate cancer by methylation and histone methylation (Shinojima et al 2012). In sporadic breast tumors, P16, MGMT, VHL, MLH1, and BRCA1 have also been shown to be important as prognostic factors (Bosviel et al 2012), and all are DNA repair and tumor suppressor genes that have been demonstrated to be epigenetically inactivated by DNA methylation in cancers. RASSF1A hypermethylation is associated with a shorter recurrence time, in ovarian, or thyroid tumors (Schagdarsurengin et al 2009, Buckingham et al 2010, Brzezianska & Pastuszak-Lewandoska 2011.…”

Section: Ovarian Cancer Stromal Tumors (Frequency !3%)mentioning

confidence: 99%

Epigenetic alterations in endocrine-related cancer

Rodríguez-Rodero¹,

Delgado²,

Fernández³

et al. 2014

Endocrine-Related Cancer

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Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

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“…The detection of methylated BRCA1 promoter in DNA from normal tissue has suggested the association of this epigenetic defect with the development of BRCA1-like breast cancer [25]. Several studies have reported the detection of methylated BRCA1 in very young breast cancer patients [26] as well as in healthy females [25,[27][28][29][30][31] suggesting the potential use of methylated BRCA1 as a predictor of cancer risk.…”

Section: Journal Of Clinical Epigenetics Issn 2472-1158mentioning

confidence: 99%

MicroRNA-126 is Dysregulated in Cancer- Free Females Harboring Methylated BRCA1 Promoter through Up-Regulation of DNMTs

Al‐Moghrabi¹,

Al‐Yousef²,

Al‐Showimi³

et al. 2017

J Clin Epigenet

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BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls

Cited by 54 publications

References 26 publications

Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients

Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients

Epigenetic alterations in endocrine-related cancer

MicroRNA-126 is Dysregulated in Cancer- Free Females Harboring Methylated BRCA1 Promoter through Up-Regulation of DNMTs

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