Genome-Wide Gene Expression Analyses of <i>BRCA1</i>- and <i>BRCA2</i>-Associated Breast and Ovarian Tumours

• Main Authors: George A. R. Wiggins, Logan C. Walker, John F. Pearson
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Cancers
• Subjects: breast cancer; ovarian cancer; microarray; gene expression; familial cancer
• Online Access: https://www.mdpi.com/2072-6694/12/10/3015

Germline pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> increase cumulative lifetime risk up to 75% for breast cancer and 76% for ovarian cancer. Genetic testing for <i>BRCA1</i> and <i>BRCA2</i> pathogenic variants has become an important part of clinical practice for cancer risk assessment and for reducing individual risk of developing cancer. Genetic testing can produce three outcomes: positive (a pathogenic variant), uninformative (no pathogenic variant) and uncertain significance (a variant of unknown clinical significance). More than one third of <i>BRCA1</i> and <i>BRCA2</i> variants identified have been classified as variants of uncertain significance, presenting a challenge for clinicians. To address this important clinical challenge, a number of studies have been undertaken to establish a gene expression phenotype for pathogenic <i>BRCA1</i> and <i>BRCA2</i> variant carriers in several diseased and normal tissues. However, the consistency of gene expression phenotypes described in studies has been poor. To determine if gene expression analysis has been a successful approach for variant classification, we describe the design and comparability of 23 published gene expression studies that have profiled cells from <i>BRCA1</i> and <i>BRCA2</i> pathogenic variant carriers. We show the impact of advancements in expression-based technologies, the importance of developing larger study cohorts and the necessity to better understand variables affecting gene expression profiles across different tissue types.