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

Tomoko Yoshihama,Kensuke Sakai,Akira Hirasawa,Kaori Kameyama,Teruhiko Yoshida,Arisa Ueki,Mineko Ushiama,Nobuyuki Susumu,Tomoko Akahane,Wataru Yamagami,Takeshi Makabe,Yoshiko Nanki,Daisuke Aoki,Kokichi Sugano,Kenjiro Kosaki

doi:10.1007/s13691-020-00449-9

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.

Highlights

During recent years, there has been a rapid advance in genetic testing techniques such as next-generation sequencing, and they are being increasingly used in clinical practice, rather than conventional single-gene analysis [1]
We present a case of an individual suspected of having Lynch syndrome, but multigene panel testing revealed that the patient was a carrier of a BRCA2 pathogenic variant
The patient had a BRCA2 pathogenic variant, and information regarding the future risk of breast, ovarian, and pancreatic cancers was collected

Summary

Introduction

There has been a rapid advance in genetic testing techniques such as next-generation sequencing, and they are being increasingly used in clinical practice, rather than conventional single-gene analysis [1]. Multigene panel testing by next-generation sequencing enables simultaneous analysis of multiple genes of interest at a lower cost than conventional techniques [2,3,4,5] In some cases, this tool has provided valuable information that has enabled to change clinical management strategies for patients [6]. As the patient was never pregnant and hoped to preserve her fertility, medroxyprogesterone acetate therapy was carried out, instead of hysterectomy As her tumor recurred when she was 49 years old, as revealed by the cytological analysis (Fig. 1), total laparoscopic hysterectomy and bilateral salpingectomy were performed, but the bilateral ovaries were not resected according to her wish. The attending physician suggested hereditary involvement, and genetic counseling was provided based on informed consent when she was 56 years old She was suspected of having Lynch syndrome because of her history of endometrial cancer and family history of colorectal cancer.

Results

Discussion

Compliance with ethical standards