| Title: |
Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer |
| Authors: |
Brouwer, Jan; Kluiver, Joost; de Almeida, Rodrigo C.; Modderman, Rutger; Terpstra, Martijn; Kok, Klaas; Withoff, Sebo; Hollema, Harry; Reitsma, Welmoed; de Bock, Geertruida H.; Mourits, Marian J. E.; van den Berg, Anke |
| Source: |
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 2016, 'Small RNA sequencing reveals a comprehensive miRNA signature of BRCA1-associated high-grade serous ovarian cancer', Journal of Clinical Pathology, vol. 69, no. 11, pp. 979-985. https://doi.org/10.1136/jclinpath-2016-203679 |
| Publication Year: |
2016 |
| Collection: |
University of Groningen research database |
| Subject Terms: |
OVARIAN TUMOUR; MOLECULAR ONCOLOGY; FALLOPIAN TUBE; SALPINGO-OOPHORECTOMY; CELL-DIVISION; CARCINOMA; MUTATIONS; MIR-145; WOMEN; METASTASIS; EXPRESSION; MICRORNAS; SURVIVAL |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0021-9746 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/27048682; info:eu-repo/semantics/altIdentifier/wos/000388006000007; info:eu-repo/semantics/altIdentifier/hdl/https://hdl.handle.net/11370/26b91b07-4dd5-4e12-b3e7-2cc88a51c0b0; info:eu-repo/semantics/altIdentifier/pissn/0021-9746 |
| DOI: |
10.1136/jclinpath-2016-203679 |
| Availability: |
https://hdl.handle.net/11370/26b91b07-4dd5-4e12-b3e7-2cc88a51c0b0; https://research.rug.nl/en/publications/26b91b07-4dd5-4e12-b3e7-2cc88a51c0b0; https://doi.org/10.1136/jclinpath-2016-203679; https://pure.rug.nl/ws/files/97626148/Small_RNA_sequencing_reveals_a_comprehensive_miRNA_signature_of_BRCA1_associated.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; https://www.rug.nl/library/open-access/article-25fa-pilot-end-user-agreement |
| Accession Number: |
edsbas.F794657 |
| Database: |
BASE |