Aberrant epigenetic and transcriptional events associated with breast cancer risk

• Published in: Clinical epigenetics 2022-02, Vol.14 (1), p.21-21, Article 21
• Main Authors: Marino, Natascia, German, Rana, Podicheti, Ram, Rusch, Douglas B, Rockey, Pam, Huang, Jie, Sandusky, George E, Temm, Constance J, Althouse, Sandra, Nephew, Kenneth P, Nakshatri, Harikrishna, Liu, Jun, Vode, Ashley, Cao, Sha, Storniolo, Anna Maria V
• Format: Article
• Language: English
• Subjects: Adult; Age; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biopsy; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - physiopathology; Cancer; Cell adhesion; Cell cycle; Cohort Studies; Deoxyribonucleic acid; Diagnosis; Disease susceptibility; DNA; DNA damage; DNA methylation; DNA Methylation - genetics; DNA Methylation - physiology; DNA microarrays; Donation of organs, tissues, etc; Epigenesis, Genetic - genetics; Epigenetic inheritance; Epigenetics; Epithelial cells; Female; Gene amplification; Gene expression; Gene loci; Genes; Genetic aspects; Genetic research; Genetic transcription; Genome-wide association studies; Genome-Wide Association Study - methods; Genome-Wide Association Study - statistics & numerical data; Genomes; Health aspects; Humans; Kinases; Methylation; Middle Aged; Oncology, Experimental; Proteins; Risk assessment; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Risk factors; Transcription; Transcriptional Activation - genetics; Transcriptional Activation - physiology; Transcriptomes; Transcriptomics; Women; Womens health
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-022-01239-1

Genome-wide association studies have identified several breast cancer susceptibility loci. However, biomarkers for risk assessment are still missing. Here, we investigated cancer-related molecular changes detected in tissues from women at high risk for breast cancer prior to disease manifestation. Disease-free breast tissue cores donated by healthy women (N = 146, median age = 39 years) were processed for both methylome (MethylCap) and transcriptome (Illumina's HiSeq4000) sequencing. Analysis of tissue microarray and primary breast epithelial cells was used to confirm gene expression dysregulation. Transcriptomic analysis identified 69 differentially expressed genes between women at high and those at average risk of breast cancer (Tyrer-Cuzick model) at FDR