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Dergiler / Experimed / 2026 / Volume: 16 Issue: 2

DNA Methylation Signatures Distinguish Breast Cancer Histological Subtypes and Predict Hormone Receptor Status: A TCGA-Based Integrative Analysis

Özkan Özdemir(ACIBADEM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF BASIC SCIENCES, DEPARTMENT OF MEDICAL BIOLOGY)0000-0002-2647-6416
Eylül Aydın(ACIBADEM MEHMET ALI AYDINLAR UNIVERSITY, GRADUATE SCHOOL OF NATURAL AND APPLIED SCIENCES, MOLECULAR AND TRANSLATIONAL BIOMEDICINE (MASTER) (WITH THESIS) (ENGLISH))0009-0005-3982-5303
Turna Demirci(ACIBADEM UNIVERSITY, GRADUATE SCHOOL OF HEALTH SCIENCES, DEPARTMENT OF TRANSLATIONAL MEDICINE)0000-0003-4971-7494
Karen Telciyan(ACIBADEM UNIVERSITY, GRADUATE SCHOOL OF HEALTH SCIENCES, DEPARTMENT OF GENOME STUDIES)0009-0003-4877-8997
Alper Akkuş(ACIBADEM MEHMET ALI AYDINLAR UNIVERSITY, GRADUATE SCHOOL OF NATURAL AND APPLIED SCIENCES, MOLECULAR AND TRANSLATIONAL BIOMEDICINE (MASTER) (WITH THESIS) (ENGLISH))0009-0005-8696-0284
Emrah Yücesan(ISTANBUL UNIVERSITY-CERRAHPASA, INSTITUTE OF NEUROLOGICAL SCIENCES, DEPARTMENT OF NEUROLOGICAL SCIENCES)0000-0003-4512-8764
Yeşim Eralp(ACIBADEM MEHMET ALI AYDINLAR UNIVERSITY, SENOLOGY RSEARCH INSTITUTE)0000-0001-9603-4755
Ozden Hatırnaz Ng(ACIBADEM MEHMET ALI AYDINLAR UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF BASIC MEDICAL SCIENCES (MEDICINE), DEPARTMENT OF MEDICAL BIOLOGY)0000-0001-7728-6527
Sayfa
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Yayın Tarihi
2026-08-28
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Compact CpG probe panels predict hormone receptor status with high accuracy in internal cross-validation, suggesting the potential of methylation-based diagnostic assays as a complementary approach to immunohistochemistry (IHC), pending external validation.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Objective: DNA methylation alterations contribute to breast cancer heterogeneity, yet their utility for distinguishing histological subtypes remains underexplored.
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Temel Bulgular & Veri:Materials and Methods: HumanMethylation450 (HM450) data from 99 samples (40 infiltrating ductal carcinoma (IDC), 40 infiltrating lobular carcinoma (ILC), 14 metaplastic, 5 medullary) and 1,098 clinical samples from The Cancer Genome Atlas (TCGA) breast invasive carcinoma (BRCA) were analyzed.
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Sonuç & Katkı:Compact CpG probe panels predict hormone receptor status with high accuracy in internal cross-validation, suggesting the potential of methylation-based diagnostic assays as a complementary approach to immunohistochemistry (IHC), pending external validation.
🔬Tür:Research Article
📍Kapsam:99 samples
⚙️Değişkenler:DNA methylation · Breast neoplasms · Machine learning

Abstract

Objective: DNA methylation alterations contribute to breast cancer heterogeneity, yet their utility for distinguishing histological subtypes remains underexplored. This study aimed to identify genome-wide methylation signatures across breast cancer subtypes and develop compact probe panels for molecular classification. Materials and Methods: HumanMethylation450 (HM450) data from 99 samples (40 infiltrating ductal carcinoma (IDC), 40 infiltrating lobular carcinoma (ILC), 14 metaplastic, 5 medullary) and 1,098 clinical samples from The Cancer Genome Atlas (TCGA) breast invasive carcinoma (BRCA) were analyzed. Differentially methylated positions (DMPs) were identified using limma with Benjamini-Hochberg false discovery rate correction. Support vector machine classifiers with minimal probe panels were developed for hormone receptor endpoints. Results: Of the 404,059 quality-filtered CpG probes, 88,909 (22.0%) were differentially methylated across subtypes (False discovery rate (FDR)<0.05). The ILC-metaplastic comparison yielded the largest divergence (58,661 DMPs). Classifiers achieved area under the curve (AUC) values of 0.935, 0.934, and 0.866 for estrogen receptor (ER), triple-negative breast cancer (TNBC), and progesterone receptor (PR) status, respectively, using 8-bit polymerase chain reaction (PCR). Fifteen CpG probes in internal cross-validation. Conclusion: Histological subtypes harbor distinct methylation landscapes dominated by global hypomethylation in metaplastic carcinoma. Compact CpG probe panels predict hormone receptor status with high accuracy in internal cross-validation, suggesting the potential of methylation-based diagnostic assays as a complementary approach to immunohistochemistry (IHC), pending external validation.

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Bu Makaleye Atıf Yap

Özdemir, Ö., Aydın, E., Demirci, T., Telciyan, K., Akkuş, A., Yücesan, E., Eralp, Y., Ng, O. H. (2026). DNA Methylation Signatures Distinguish Breast Cancer Histological Subtypes and Predict Hormone Receptor Status: A TCGA-Based Integrative Analysis. Experimed, Volume: 16 Issue: 2. https://doi.org/10.26650/experimed.1930098

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