Germline heterozygous exons 8–11 pathogenic BARD1 gene deletion reported for the first time in a family with suspicion of a hereditary colorectal cancer syndrome: more than an incidental finding?

Hereditary Cancer in Clinical Practice

Case Report

Sergio Carrera¹  Almudena Callejo²  Nagore Miñambres²  Alberto Muñoz²  Abigail Ruiz de Lobera²  Pablo Jiménez-Labaig²  Ana Belén Rodríguez-Martínez³  Esther Sarasola³  Intza Garin⁴  Hiart Maortua⁴  Cristina Martínez⁴ 

[1]Hereditary Cancer Genetic Counseling Unit- Medical Oncology Department, Cruces University Hospital, Plaza de Cruces S/N. 48903, Baracaldo, Bizkaia, Spain

[2]Medical Oncology Department, Cruces University Hospital, Baracaldo, Spain

[3]Molecular Genetics Laboratory, Basurto University Hospital, Bilbao, Spain

[4]Molecular Genetics Laboratory, Cruces University Hospital, Baracaldo, Spain

关键词: Colorectal cancer;    Hereditary;    BARD1;    Pathogenic variant;    Deletion;    Amsterdam clinical criteria;    Familial colorectal cancer type X syndrome;    Cancer genetic counseling;   

DOI  :  10.1186/s13053-023-00246-4

 received in 2022-10-21, accepted in 2023-01-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) is a highly prevalent disease in developed countries. Inherited Mendelian causes account for approximately 5% of CRC cases, with Lynch syndrome and familial adenomatous polyposis being the most prevalent forms. Scientific efforts are focused on the discovery of new candidate genes associated with CRC and new associations of phenotypes with well-established cancer-related genes. BRCA1-associated ring domain (BARD1) gene deleterious germline variants are associated with a moderate increase in the relative risk of breast cancer, but their association with other neoplasms, such as CRC, remains unclear.Case presentationWe present the case of a 49-year-old male diagnosed with rectal adenocarcinoma whose maternal family fulfilled Amsterdam clinical criteria for Lynch syndrome. Genetic test confirmed the presence in heterozygosis of a germline pathogenic deletion of exons 8–11 in BARD1 gene. The predictive genetic study of the family revealed the presence of this pathogenic variant in his deceased cancer affected relatives, confirming co-segregation of the deletion with the disease.ConclusionsTo the best of our knowledge, this is the first published work in which this BARD1 deletion is detected in a family with familial colorectal cancer type X (FCCTX) syndrome, in which the clinical criteria for Lynch syndrome without alteration of the DNA mismatch repair (MMR) system are fulfilled. Whether this incidental germline finding is the cause of familial colorectal aggregation remains to be elucidated in scientific forums. Patients should be carefully assessed in specific cancer genetic counseling units to account for hypothetical casual findings in other genes, in principle unrelated to the initial clinical suspicion, but with potential impact on their health.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 61