Identification of a large intra-exonic deletion in BRCA2 exon 18 in a pancreatic ductal adenocarcinoma

Inès Debbabi; Sophie Vacher; Cindy Neuzillet; Jérome Cros; Françoise Revillon; Ambre Petitalot; Anthony Turpin; Samantha Antonio; Elodie Girard; Célia Dupain; Maud Kamal; Pascal Hammel; Ivan Bièche; Julien Masliah-Planchon; Sandrine M Caputo

doi:10.1177/17588359221146132

Identification of a large intra-exonic deletion in BRCA2 exon 18 in a pancreatic ductal adenocarcinoma

Ther Adv Med Oncol. 2023 Jan 18:15:17588359221146132. doi: 10.1177/17588359221146132. eCollection 2023.

Authors

Inès Debbabi¹, Sophie Vacher^{1

2}, Cindy Neuzillet³, Jérome Cros^{4

5}, Françoise Revillon⁶, Ambre Petitalot^{1

2}, Anthony Turpin^{7

8}, Samantha Antonio^{1

2}, Elodie Girard⁹, Célia Dupain¹⁰, Maud Kamal¹⁰, Pascal Hammel¹¹, Ivan Bièche^{1

12}, Julien Masliah-Planchon^{1

2}, Sandrine M Caputo^{1

13}

Affiliations

¹ Department of Genetics, Institut Curie, Paris, France.
² PSL Research University, Paris, France.
³ Department of Medical Oncology, Curie Institute, Versailles Saint Quentin University, Paris, France.
⁴ INSERM UMR1149, Beaujon University Hospital, Paris University, Paris, France.
⁵ Department of Pathology, Beaujon University, Hospital Paris 7 Diderot University, Paris, France.
⁶ Unit of Human Molecular Oncology, Centre Oscar Lambret, Lille, France.
⁷ ULR9020-UMR-S 1277 Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, France.
⁸ Medical Oncology Department, CHU Lille, University of Lille, France.
⁹ INSERM UMR1149, Institut Curie, Paris, France.
¹⁰ Department of Drug Development and Innovation, Institut Curie, PSL Research University, Paris.
¹¹ Department of Digestive and Medical Oncology, Paris-Saclay University, Hôpital Paul Brousse, Villejuif, France.
¹² Université de Paris, Paris, France.
¹³ PSL Research University, 75005 Paris, France.

Abstract

By 2030, pancreatic cancer will become the second leading cause of cancer-related deaths in the United States and in Europe. The management of patients with advanced pancreatic cancer relies on chemotherapy and poly (ADP-ribose) polymerase inhibitors for patients who carry BRCA1/2 inactivating alterations. Some variants, such as large insertion/deletions (Indels), inactivating BRCA1/2 and therefore of clinical relevance can be hard to detect by next-generation sequencing techniques. Here we report a 47-year-old patient presenting with pancreatic cancer whose tumour harbours a large somatic intra-exonic deletion of BRCA2 of 141 bp. This BRCA2 deletion, located in the C-terminal domain, can be considered as pathogenic and consequently affect tumorigenesis because it is involved in the interaction between the DSS1 protein and DNA. Thanks to the optimized bioinformatics algorithm, this intermediate size deletion in BRCA2 was identified, enabling personalized patient management via the inclusion of the patients in a clinical trial.

Keywords: BRCA2; deletion; pancreatic cancer; rearrangement; variant of unknown significance.

Publication types

Case Reports