RESUMEN
In the original publication, part d of Figure 2 was mistakenly not included.
RESUMEN
Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1, MSH2, MSH6, and PMS2) encoding mismatch repair proteins. Being located immediately upstream of the MSH2 gene, EPCAM abnormalities can affect MSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication. MSH2 forms heterodimers with MSH6 or MSH3 (MutSα, MutSß, respectively) and is involved in mismatch-pair recognition and initiation of repair. MLH1 forms a complex with PMS2, and functions as an endonuclease. If the mismatch repair system is thoroughly working, genome integrity is maintained completely. Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors. Children with germline biallelic mismatch repair gene abnormalities were reported to develop conditions such as gastrointestinal polyposis, colorectal cancer, brain cancer, leukemia, etc., and so on, demonstrating the need to respond with new concepts in genetic counseling. In promoting cancer genome medicine in a new era, such as by utilizing immune checkpoints, it is important to understand the genetic and genomic molecular background, including the status of mismatch repair deficiency.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/fisiología , Neoplasias Encefálicas/genética , Niño , Reparación de la Incompatibilidad de ADN/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/genética , Molécula de Adhesión Celular Epitelial/genética , Femenino , Asesoramiento Genético , Pruebas Genéticas , Humanos , Inestabilidad de Microsatélites , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Homólogo 1 de la Proteína MutL/genética , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , MutaciónRESUMEN
A majority of breast cancer (BC) molecular subtype in BRCA1 variants carriers is triple-negative type. In contrast, human epidermal growth factor 2 (HER2)-positive BC among carriers of BRCA1 variants is rarely reported. A 42-year-old woman who previously received adjuvant endocrine therapy against left BC developed a left BC relapse and a right new primary BC. Her mother had BC and ovary cancer, and her cousin had BC. Genetic testing revealed a pathogenic large deletion of exons 1-8 in BRCA1. She was diagnosed with hereditary breast and ovary cancer and underwent bilateral mastectomy. The molecular subtypes of her right and left primary BC were HER2-enriched type and luminal-HER2 type, respectively. After completion of adjuvant therapy for right BC, risk-reducing salpingo-oophorectomy (RRSO) is planned. The present case makes us consider the frequency of BRCA1 large rearrangements in Japanese, the association between HER2 amplification and BRCA1 variants, and the optimal timing of RRSO in patients receiving adjuvant therapy for BC.