BRCA1; case report; colorectal (colon) cancer; exome sequencing (ES); homologous recombination deficiency (HRD); Oncology; Cancer Research
Abstract :
[en] 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.
Disciplines :
Oncology
Author, co-author :
Freire, Maria Valeria ; Department of Human Genetics, GIGA Research Center - University of Liège and Centre Hospitalier Universitaire (CHU) Liège, Liège, Belgium
MARTIN, Marie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Thissen, Romain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine
Van Marcke, Cédric; 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, Karin ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
SEPULCHRE, Edith ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
LEROI, Natacha ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
LETE, Céline ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
FASQUELLE, Corinne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Radermacher, Jean; Department of Pathology, Institut de Pathologie et de Génétique, Charleroi, Belgium
Gokburun, Yeter; Department of Gastroenterology, Centre Hospitalier Régional Sambre et Meuse, Namur, Belgium
COLLIGNON, Joëlle ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Sacré, Anne ; Université de Liège - ULiège > Département des sciences de la vie > Phylogénomique des eucaryotes ; Onco-Hematology Department, Centre Hospitalier Régional (CHR) Verviers, Verviers, Belgium
JOSSE, Claire ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
PALMEIRA, Léonor ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
BOURS, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
This work was supported by a Télévie fellowship (MV.F., grant N° 7451419F), a grant from the CHU Liége (N° 981481200) and the WALGEMED grant (Région Wallonne, grant N° 1710180).
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