Case Report Series: Aggressive HR Deficient Colorectal Cancers Related to BRCA1 Pathogenic Germline Variants.

Autor:	Freire MV; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Martin M; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Thissen R; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Van Marcke C; Institute for Experimental and Clinical Research (Institut de Recherche Expérimentale et Clinique (IREC), Pôle Molecular Imaging, Radiotherapy and Oncology (MIRO)), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.; Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium., Segers K; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Sépulchre E; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Leroi N; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Lété C; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Fasquelle C; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Radermacher J; Department of Pathology, Institut de Pathologie et de Génétique, Charleroi, Belgium., Gokburun Y; Department of Gastroenterology, Centre Hospitalier Régional Sambre et Meuse, Namur, Belgium., Collignon J; Department of Medical Oncology, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Sacré A; Onco-Hematology Department, Centre Hospitalier Régional (CHR) Verviers, Verviers, Belgium., Josse C; Department of Medical Oncology, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Palmeira L; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium., Bours V; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Feb 24; Vol. 12, pp. 835581. Date of Electronic Publication: 2022 Feb 24 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.835581
Abstrakt:	Objective: The link between BRCA1 and homologous recombination deficiency (HRD) in cancer has gained importance with the emergence of new targeted cancer treatments, while the available data on the role of the gene in colorectal cancer (CRC) remain contradictory. The aim of this case series was to elucidate the role of known pathogenic BRCA1 variants in the development of early-onset CRC. Design: Patients were evaluated using targeted next generation sequencing, exome sequencing and chromosomal microarray analysis of the paired germline and tumor samples. These results were used to calculate the HRD score and the frequency of mutational signatures in the tumors. Results: Three patients with metastatic CRC were heterozygous for a previously known BRCA1 nonsense variant. All tumors showed remarkably high HRD scores, and the HRD-related signature 3 had the second highest contribution to the somatic pattern of variant accumulation in the samples (23% in 1 and 2, and 13% in sample 3). Conclusions: A BRCA1 germline pathogenic variant can be involved in CRC development through HRD. Thus, BRCA1 testing should be considered in young patients with a personal history of microsatellite stable CRC as this could further allow a personalized treatment approach. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Freire, Martin, Thissen, Van Marcke, Segers, Sépulchre, Leroi, Lété, Fasquelle, Radermacher, Gokburun, Collignon, Sacré, Josse, Palmeira and Bours.)
Databáze:	MEDLINE
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