Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey.

In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.

Establishment of in-hospital clinical network for patients with neurofibromatosis type 1 in Nagoya University Hospital.

Neurofibromatosis type 1 (NF1) is a genetic multisystem disorder. Clinicians must be aware of the diverse clinical features of this disorder in order to provide optimal care for it. We have set up an NF1 in-hospital medical care network of specialists regardless of patient age, launching a multidisciplinary approach to the disease for the first time in Japan. From January 2014 to December 2020, 246 patients were enrolled in the NF1 patient list and medical records. Mean age was 26.0 years ranging from 3 months to 80 years. The number of patients was higher as age at first visit was lower. There were 107 males (41%) and 139 females. After 2011, the number of patients has increased since the year when the medical care network was started. Regarding orthopedic signs, scoliosis was present in 60 cases (26%), and bone abnormalities in the upper arm, forearm, and tibia in 8 cases (3.5%). Neurofibromas other than cutaneous neurofibromas were present in 90 cases (39%), and MPNST in 17 cases (7.4%). We launched a multidisciplinary NF1 clinic system for the first time in Japan. For patients with NF1, which is a hereditary and systemic disease associated with a high incidence of malignant tumors, it will be of great benefit when the number of such clinics in Japan and the rest of Asia is increased.

Next-generation genome sequencing of a matched normal-tumor pair from a patient with intractable gestational choriocarcinoma: A case report.

Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) originating from trophoblastic cells with abnormal proliferation. Although chemotherapy is effective for treating this cancer, when patients develop chemoresistance, personalized treatment, such as the use of drugs matching their genomes, is required. The present report describes a case of intractable gestational choriocarcinoma identified using a next-generation sequencing (NGS)-based tumor panel. A 51-year-old woman was diagnosed with gestational choriocarcinoma via pathological and short tandem repeat analyses. The patient did not achieve remission despite many regimens of chemotherapy, including high-dose therapy with autologous peripheral blood stem cell transplantation. To identify drugs tailored to this particular choriocarcinoma, NGS was performed on the tumor of the patient, and the tumor genome was compared with that of the patient's blood sample using the NCC Oncopanel System. Consequently, 245 single nucleotide variants (SNVs) with a mean SNV allele frequency of 63.1% were identified. This high frequency was because the genome of the gestational choriocarcinoma contained part of the genome of the partner. Therefore, our experience of the present intractable case of choriocarcinoma suggested that matched normal-tumor pair analysis is not appropriate for treatment decisions in GTN cases. When using an NGS-based tumor panel to assess choriocarcinoma, researchers must consider whether the genomic DNA of the patient and their partner are involved in the GTN.