Oncogenetics: Interdisciplinary Approach of a Clinical Case

The role played by genes in the development of cancer is an area that is advancing very fast, even more so with the advent of omics sciences. On the other hand, the comprehensive approach to the patient requires an interdisciplinary cooperation involving medical, biomedical and psychosocial specialties. Mainly, the impact assessment of the genetic test results on the patient and their family. Furthermore, it is important for decision-making about prevention, early diagnosis and availability of treatment. As well as on aspects related to their social, familiar and emotional life. The initiation and progression of cancer is a complex biological system that involves genomic, epigenomic, proteomic alterations and the relationship between tumor cells and their tissue microenvironment. Most cancers are sporadic, but about 5-10% are classified as hereditary cancer because they are caused by germline mutations in genes related to the carcinogenic process. However, a mutation is not identified in specific predisposing genes in about 15-20% of women diagnosed with breast cancer, despite of a known family history of the disease. We report a case of a 36-year-old woman, derived by the oncologist, with a unilateral invasive breast carcinoma associated with fibrocystic mastopathy. Immunohistochemistry reported: estrogen receptor: positive; progesterone receptor: positive; human epidermal growth factor type 2 HER2/neu (c-erbB-2): negative and the cell proliferation marker Ki67: positive. Personal and family history of the patient was evaluated and requested a hereditary cancer panel covering 199 genes. Two heterozygous frameshift pathogenic variants were identified in two tumor suppressor genes. These variants change the reading frame producing a premature stop codon that results in a non -functional or truncated protein. The involved genes were: the breast cancer gene BRCA2 located on chromosome13q13.1 which encodes a protein that acts in DNA repairing; and the checkpoint kinase 2 gene CHEK2 located on chromosome 22q12.1 which encodes a protein that control the cell cycle driving apoptosis. The variants in heterozygosis in BRCA2 have been associated with an increased risk for hereditary breast and ovarian cancer syndrome. This syndrome is inherited in an autosomal dominant pattern. It is characterized by a high risk of breast and ovarian cancers within the same family group. Based on the genetic findings, the psychological impact on the patient and the assessment of her