Jasmine Sukumar1, Mahmoud Kassem1, Doreen Agnese2, Robert Pilarski3, Bhuvaneswari Ramaswamy1, Kevin Sweet3, Sagar Sardesai4. 1. Division of Medical Oncology, The Ohio State University Wexner Medical Center, 1204A Lincoln Tower, 1800 Cannon Dr., Columbus, OH, 43210, USA. 2. Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA. 3. Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA. 4. Division of Medical Oncology, The Ohio State University Wexner Medical Center, 1204A Lincoln Tower, 1800 Cannon Dr., Columbus, OH, 43210, USA. Sagar.Sardesai@osumc.edu.
Abstract
BACKGROUND: Concurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer. Case presentation The proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants in BRCA1 (c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient's two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1 (c.181T > G) and CHEK2 (1100delC) genes. CONCLUSION: The cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.
BACKGROUND: Concurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer. Case presentation The proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants in BRCA1 (c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient's two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1 (c.181T > G) and CHEK2 (1100delC) genes. CONCLUSION: The cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.
Entities:
Keywords:
BRCA1; BRCA2; Breast cancer; CHEK2; DNAI1; Genetic; Germline; Variants