Identification of Breast Cancer DNA Methylation Markers Optimized for Fine-Needle Aspiration Samples

Bu, Dawei; Lewis, Cheryl; Sarode, Venetia; Chen, Min; Ma, Xiaotu; Lazorwitz, Aaron; Rao, Roshni; Leitch, Marilyn; Moldrem, Amy; Andrews, Valerie; Gazdar, Adi F.; Euhus, David M.

doi:10.1158/1055-9965.epi-13-0208

Cited by 13 publications

(9 citation statements)

References 37 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From the seven most promising candidates, six ( APC , CCND2 , FOXA1 , PSAT1 , RASSF1A and SCGB3A1 ) confirmed its cancer-specificity, discriminating normal from cancerous tissues, although with variable performance, paralleling previous observations from our team and others [ 8 , 9 , 38 ]. Interestingly, a panel combining APC , FOXA1 , RASSF1A and SCGB3A1 disclosed the highest accuracy for BrC detection (94%).…”

Section: Discussionsupporting

confidence: 86%

A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA

Salta

Nunes

Fontes‐Sousa

et al. 2018

JCM

View full text Add to dashboard Cite

Background: Breast cancer (BrC) is the most frequent neoplasm in women. New biomarkers, including aberrant DNA methylation, may improve BrC management. Herein, we evaluated the detection and prognostic performance of seven genes’ promoter methylation (APC, BRCA1, CCND2, FOXA1, PSAT1, RASSF1A and SCGB3A1). Methods: Methylation levels were assessed in primary BrC tissues by quantitative methylation-specific polymerase chain reaction (QMSP) and in circulating cell-free DNA (ccfDNA) by multiplex QMSP from two independent cohorts of patients (Cohort #1, n = 137; and Cohort #2, n = 44). Receiver operating characteristic (ROC) curves were constructed, and log-rank test and Cox regression were performed to assess the prognostic value of genes’ methylation levels. Results: The gene-panel APC, FOXA1, RASSF1A, SCGB3A1 discriminated normal from cancerous tissue with high accuracy (95.55%). In multivariable analysis, high PSAT1-methylation levels [>percentile 75 (P75)] associated with longer disease-free survival, whereas higher FOXA1-methylation levels (>P75) associated with shorter disease-specific survival. The best performing panel in ccfDNA (APC, FOXA1 and RASSF1A) disclosed a sensitivity, specificity and accuracy over 70%. Conclusions: This approach enables BrC accurate diagnosis and prognostic stratification in tissue samples, and allows for early detection in liquid biopsies, thus suggesting a putative value for patient management.

show abstract

Section: Discussionsupporting

confidence: 86%

A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA

Salta

Nunes

Fontes‐Sousa

et al. 2018

JCM

View full text Add to dashboard Cite

show abstract

“…Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is recognized as one of the earliest, most frequent, and robust alterations in cancer development (12,13). However, low-level methylation occurs in certain CpG regions in benign conditions (14)(15)(16)(17)(18)(19). Euhus and colleagues performed a genome-wide search for differentially methylated markers in cancer and benign breast epithelial cell lines treated with 5-azacytidine.…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Markers for Breast Cancer Detection in the Developing World

Downs

Mercado-Rodriguez

Cimino‐Mathews

et al. 2019

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: An unmet need in low-resource countries is an automated breast cancer detection assay to prioritize women who should undergo core breast biopsy and pathologic review. Therefore, we sought to identify and validate a panel of methylated DNA markers to discriminate between cancer and benign breast lesions using cells obtained by fine-needle aspiration (FNA).Experimental Design: Two case-control studies were conducted comparing cancer and benign breast tissue identified from clinical repositories in the United States, China, and South Africa for marker selection/training (N ¼ 226) and testing (N ¼ 246). Twenty-five methylated markers were assayed by Quantitative Multiplex-Methylation-Specific PCR (QM-MSP) to select and test a cancer-specific panel. Next, a pilot study was conducted on archival FNAs (49 benign, 24 invasive) from women with mammographically suspicious lesions using a newly developed, 5-hour, quantitative, automated cartridge system. We calculated sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) compared with histopathology for the marker panel.Results: In the discovery cohort, 10 of 25 markers were selected that were highly methylated in breast cancer compared with benign tissues by QM-MSP. In the independent test cohort, this panel yielded an AUC of 0.937 (95% CI ¼ 0.900-0.970). In the FNA pilot, we achieved an AUC of 0.960 (95% CI ¼ 0.883-1.0) using the automated cartridge system.Conclusions: We developed and piloted a fast and accurate methylation marker-based automated cartridge system to detect breast cancer in FNA samples. This quick ancillary test has the potential to prioritize cancer over benign tissues for expedited pathologic evaluation in poorly resourced countries.

show abstract

“…Several studies have implicated that the Copine family contributes to oncogenesis. In breast cancer, the promoter of the CPNE8 gene is more frequently methylated in hormone receptor-positive cancer compared with in hormone receptor-negative cancer, thus the difference of the methylation status may partly explain the correlation between CPNE8 expression and aggressiveness of breast cancer [31]. Since the expression of estrogen and progesterone receptors is almost negative in CCC [26], the gene expression profile of CCC might exhibit a similarity with that of triple-negative breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing

Nagasawa

Ikeda

Horie‐Inoue

et al. 2019

IJMS

View full text Add to dashboard Cite

Objective: Ovarian cancer has the highest mortality among gynecological cancers. High-grade serous carcinoma (HGSC) is the most common histotype of ovarian cancer regardless of ethnicity, whereas clear cell carcinoma (CCC) is more common in East Asians than Caucasians. The elucidation of predominant signaling pathways in these cancers is the first step towards understanding their molecular mechanisms and developing their clinical management. Methods: RNA sequencing was performed for 27 clinical ovarian specimens from Japanese women. Principal component analysis (PCA) was conducted on the sequence data mapped on RefSeq with normalized read counts, and functional annotation analysis was performed on genes with substantial weights in PCA. Knockdown experiments were conducted on the selected genes on the basis of PCA. Results: Functional annotation analysis of PCA-defined genes showed predominant pathways, such as cell growth regulators and blood coagulators in CCC and transcription regulators in HGSC. Knockdown experiments showed that the inhibition of the calcium-dependent protein copine 8 (CPNE8) and the transcription factor basic helix-loop-helix family member e 41 (BHLHE41) repressed the proliferation of CCC- and HGSC-derived cells, respectively. Conclusions: This study identified CPNE8 and BHLHE41 as characteristic genes for CCC and HGSC, respectively. The systemic identification of differentially expressed genes in CCC and HGSC will provide useful information to understand transcriptomic differences in these ovarian cancers and to further develop potential diagnostic and therapeutic options for advanced disease.

show abstract

Identification of Breast Cancer DNA Methylation Markers Optimized for Fine-Needle Aspiration Samples

Cited by 13 publications

References 37 publications

A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA

A DNA Methylation-Based Test for Breast Cancer Detection in Circulating Cell-Free DNA

DNA Methylation Markers for Breast Cancer Detection in the Developing World

Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing

Contact Info

Product

Resources

About