MicroRNA expression profiling in pelvic high-grade serous cancer of BRCA1 mutation carriers

Brouwer, J. (2014) MicroRNA expression profiling in pelvic high-grade serous cancer of BRCA1 mutation carriers. thesis, Medicine.

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Abstract

Rationale: BRCA1 carriers are predisposed of developing pelvic high-grade serous cancer (PHGSC), a malignancy which most likely originates from the fallopian tube. To gain more insight in this disease, we aimed to generate an extensive microRNA (miRNA) expression profile of PHGSC of BRCA1 carriers. We validated the results on an independent cohort of BRCA1 and non-BRCA carriers. Study design: Small RNA sequencing (Illumina 2000) was performed on 8 benign tubal samples and 5 PHGSC samples of BRCA1 carriers. Expression data was analyzed in GeneSpring and Genesis. Ten miRNAs were selected for qRT-PCR (TaqMan) validation which was performed first on the small RNA sequencing samples followed by the independent cohort. Comparisons of the independent cohort were made between BRCA1 benign (n=8) and BRCA1 PHGSC (n=11) and between non-BRCA benign (n=8) and non-BRCA PHGSC (n=12). Results: Small RNA sequencing showed 166 differentially expressed (p<0.05) miRNAs of which 143 (107 up and 36 downregulated) showed >2 fold expression and 64 (40 up and 24 downregulated) showed >4 fold expression. Principle component analysis perfectly separated the PHGSC samples from the benign samples. qRT-PCR showed the same pattern as obtained by small RNA sequencing. Independent validation confirmed deregulation in PHGSC and reached significance (p<0.05) for 7/10 miRNAs in BRCA1 PHGSC and 9/10 miRNAs non-BRCA PHGSC. Conclusion: Small RNA sequencing identified a comprehensive miRNA expression profile of PHGSC of BRCA1 carriers of which a selection was validated independently. Our findings contribute in understanding the poorly understood pathogenesis of PHGSC.

Item Type:	Thesis (Thesis)
Supervisor name:	Mourits, Prof. dr. M.J.E. and Bock, Prof. dr. G.H. de and Berg, Prof. dr. A. van den
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:59
Last Modified:	25 Jun 2020 10:59
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1917

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