title: A case of contralateral breast cancer and skin cancer associated with NBN heterozygous pathogenic variant c.698_701delAACA.
abstract: Approximately 39.6% of people will be diagnosed with cancer during their lifetime. Several factors including, lifestyle, environment and genetics may play a role in its development. Understanding these causes will greatly improve treatment methods, prevention, and survival rates of these patients. Our patient, who has a positive family history of cancer, presented with contralateral breast cancer and multiple skin malignancies. Genetic testing revealed a frameshift variant in NBN. This gene encodes the protein, nibrin, which is involved in maintaining genomic stability. Several reports have identified heterozygous NBN frameshift (c.2028delT, c.2097dupT, c.657-661delACAAA) and splice site variants (c.1397+delG) in patients with breast cancer. However, our report is the first to describe a heterozygous c.698_701delAACA NBN variant in a patient with breast cancer. Since NBN is involved in DNA integrity, loss of functional protein due to pathogenic variants significantly increases the risk of various cancers. Given the family and personal history of our patient, in connection with previous reports of NBN pathogenic variants predisposition to cancer, this variant is predicted to be pathogenic and clinically significant.
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA. gass.jennifer@mayo.edu.|Department of Clinical Genomics, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA. gass.jennifer@mayo.edu.
authors.forename: Jennifer
authors.identifier: 0000-0001-8189-4189
authors.initials: J
authors.lastname: Gass
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.|Department of Clinical Genomics, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jackson
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.|Department of Clinical Genomics, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Macklin
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blackburn
authors.affiliation: Department of Medicine, Division of Diagnostic & Consultative Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hines
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.|Department of Clinical Genomics, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL, 32224, USA.
authors.forename: Paldeep S
authors.initials: PS
authors.lastname: Atwal
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins
keywords: Breast cancer; Melanoma; NBN pathogenic variants; Nibrin; Squamous cell carcinoma