Publication

Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer

Brouwer, J., Kluiver, J., de Almeida, R. C., Modderman, R., Terpstra, M., Kok, K., Withoff, S., Hollema, H., Reitsma, W., de Bock, G. H., Mourits, M. J. E. & van den Berg, A., Nov-2016, In : Journal of Clinical Pathology. 69, 11, p. 979-985 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

AimsBRCA1 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 >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.

Original languageEnglish
Pages (from-to)979-985
Number of pages7
JournalJournal of Clinical Pathology
Volume69
Issue number11
Publication statusPublished - Nov-2016

    Keywords

  • OVARIAN TUMOUR, MOLECULAR ONCOLOGY, FALLOPIAN TUBE, SALPINGO-OOPHORECTOMY, CELL-DIVISION, CARCINOMA, MUTATIONS, MIR-145, WOMEN, METASTASIS, EXPRESSION, MICRORNAS, SURVIVAL

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