title: Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.
abstract: Intraepithelial carcinomas of the fallopian tube are putative precursors to high-grade serous carcinomas of the ovary and peritoneum. Molecular characterization of these early precursors is limited but could be the key to identifying tumor biomarkers for early detection. This study presents a genome-wide copy number analysis of occult fallopian tube carcinomas identified through risk-reducing prophylactic oophorectomy from three women with germline BRCA1 mutations, demonstrating that extensive genomic aberrations are already established at this early stage. We found no indication of a difference in the level of genomic aberration observed in fallopian tube carcinomas compared with high-grade serous ovarian carcinomas. These findings suggest that spread to the peritoneal cavity may require no or very little further tumor evolution, which raises the question of what is the real window of opportunity to detect high-grade serous peritoneal carcinoma arising from the fallopian tube before it spreads. Nonetheless, the similarity of the genomic aberrations to those observed in high-grade serous ovarian carcinomas suggests that genetic biomarkers identified in late-stage disease may be relevant for early detection.
authors.affiliation: Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Hunter
authors.affiliation: Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Ryland
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Phillip
authors.initials: P
authors.lastname: Moss
authors.affiliation: Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia; Department of Pathology, University of Melbourne, Parkville, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
authors.affiliation: Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia; Department of Pathology, University of Melbourne, Parkville, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. Electronic address: ian.campbell@petermac.org.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D002869:Chromosome Aberrations; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human