PT - JOURNAL ARTICLE AU - Brouwer, Jan AU - Kluiver, Joost AU - de Almeida, Rodrigo C AU - Modderman, Rutger AU - Terpstra, Miente Martijn AU - Kok, Klaas AU - Withoff, Sebo AU - Hollema, Harry AU - Reitsma, Welmoed AU - de Bock, Geertruida H AU - Mourits, Marian J E AU - van den Berg, Anke TI - Small RNA sequencing reveals a comprehensive miRNA signature of <em>BRCA1</em>-associated high-grade serous ovarian cancer AID - 10.1136/jclinpath-2016-203679 DP - 2016 Nov 01 TA - Journal of Clinical Pathology PG - 979--985 VI - 69 IP - 11 4099 - http://jcp.bmj.com/content/69/11/979.short 4100 - http://jcp.bmj.com/content/69/11/979.full SO - J Clin Pathol2016 Nov 01; 69 AB - Aims BRCA1 mutation carriers are at increased risk of developing high-grade serous ovarian cancer (HGSOC), a malignancy that originates from fallopian tube epithelium. We aimed to identify differentially expressed known and novel miRNAs in BRCA1-associated HGSOC.Methods Small RNA sequencing was performed on eight normal tubal and five HGSOC samples of BRCA1 carriers. Differential expression of a subset of known and novel miRNAs was validated by qRT-PCR on the samples used for small RNA sequencing and a second sample cohort comprising normal and HGSOC tissue of matched BRCA1 and non-BRCA carriers. Data from The Cancer Genome Atlas were used to determine the clinical relevance of the validated differentially expressed miRNAs.Results 59 known and 20 novel miRNAs showed a significant &gt;fourfold expression difference between normal tubal tissue and HGSOC. qRT-PCR validation confirmed a significant difference in expression levels for 10 out of 11 known miRNAs. Upregulation of two novel miRNAs could not be confirmed. Interestingly, for seven miRNAs a significant increase in expression was observed when comparing normal tubal tissue of postmenopausal women with premenopausal women. Expression levels of miR-145-5p significantly increased with International Federation of Gynecology and Obstetrics stage, while the expression levels of the other nine validated miRNAs were not associated with clinical characteristics.Conclusions We report a comprehensive expression signature including both known and novel miRNAs of BRCA1-associated HGSOC. Comparison with previous profiling studies showed a good overlap and a large number of miRNAs not reported to be differentially expressed in HGSOC before underscoring the importance of this study.