Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome

Abstract

There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer.

MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature

“…The sensitivity and specificity of IHC in patients with MMR mutations are 83% and 89%, respectively[ 42 ]. When IHC results suggest deleting MLH1 and PMS2 proteins, universal screening including BRAF testing and MLH1 promoter methylation analysis is required[ 10 , 22 , 24 , 25 , 28 , 38 - 40 , 43 , 44 ]. In the present study, the IHC results showed the loss of MLH1 and PMS2 proteins, but expression of MSH2 and MSH6 proteins in the tumor cells.…”

Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

“…GRCh37/hg19 was used for data analysis as the human reference genome assembly in the PreSSision Exome test. Germline panel testing using the OncoGuide NCC Oncopanel System FC v. 1.0 (Agilent, Tokyo, Japan) was performed as previously described [ 12 ], and GRCh38/hg38 was used for data analysis as the human reference genome assembly. MLPA using a kit purchased from MRC-Holland (Amsterdam, the Netherlands) was performed as previously described, according to the manufacturer’s recommendations [ 13 ], and GRCh37/hg19 was used for data analysis as the human reference genome assembly.…”

Genetic Counseling System for Multi-Gene Panel Testing

“…Health Educ Public Health 2021, 4:2 reditary tumors [15]. Yoshihama et al reported a case in Japan where HBOC could not be diagnosed without MGP [16]. On the other hand, according to a paper by Yurgelun MB [17], 37% of the cases in which a pathological variant was found as a result of performing MGP in suspected Lynch syndrome cases showed a pathological variant other than the Lynch syndrome-related gene [18].…”