Sayaka Ueno

Abstract Background Online genetic care can offer a promising solution to the shortage of qualified medical professionals in genetic medicine, which leads to regional disparities in access. However, despite global adoption, its use in Japan remains limited. Methods Two questionnaire surveys were conducted to investigate potential needs and barriers regarding online genetic care: one involving 858 medical professionals (738 physicians and 120 genetic counselors or nurses), and the other involving 443 clients who received in-person genetic counseling. Results Only 14.0% of the medical professionals had experience with online genetic care, although 85.9% of the professionals engaged in cancer genetics were willing to consider providing it in the future. Notably, a discrepancy was found regarding hospital selection: clients prioritized access to specialized medical care, whereas professionals assumed clients valued accessibility for family members. Professionals expressed greater concerns about adequacy of online communication, client environments and internet security. Among clients, 89.1% estimated they would sufficiently understand and accept total content of counseling session if were conducted online. Older age and infrequent internet use were associated with lower acceptance and higher anxiety regarding online methods. Concerns about ability to use the necessary technology affected clients’ willingness to encourage online care for their relatives. Conclusion Online genetic care shows high potential for client acceptance and can effectively address regional disparities in Japan. To bridge the gap between client needs and professional perceptions and to overcome the digital divide, it is necessary to develop secure, accessible systems and provide education for both patients and healthcare providers.

BACKGROUND: Comprehensive genomic profiling (CGP) has been used to identify mutations in several hundred cancer-related genes. Patients may receive treatment that targets specific genetic mutations revealed by CGP. This study aimed to investigate the usefulness of CGP in gynecologic malignancies. METHODS: Hospital records including CGP and clinical information were reviewed from 20 institutions in the Kinki District of Japan for patients with gynecological malignancies who underwent CGP. RESULTS: A total of 724 patients were included, of whom 162 had cervical cancer, 157 had endometrial cancer, 327 had ovarian cancer, 29 had other cancers, and 49 had sarcomas. Actionable gene alterations were identified in 370 (51.1%). The most commonly altered genes were PIK3CA (14.4%), high loss of heterozygosity (12.4%), and high tumor mutation burden (10.9%). Matched therapy, based on actionable gene alterations, was administered to 73 patients (10.1%). Of these, 23 patients received matched therapy for a high tumor mutation burden, 10 for high microsatellite instability and BRCA1/2, six for ERBB2, and five for PIK3CA. Twenty-five patients died before receiving their CGP results. The objective response and disease control rates were 23.6% and 41.8%, respectively. Of the 122 patients to whom genetic counseling was recommended, 68 accepted. CONCLUSIONS: CGP testing for gynecological malignancies in Japan may improve therapeutic efficacy. However, several issues remain to be addressed, including the low matched therapy rate and death prior to availability of CGP test results.

BACKGROUND: Cancer gene panel testing (CGP) helps comprehensively analyze a large number of genes, extracting genetic information from the genome profile to aid treatment plans and drug therapy. Advances in drug therapy and surgical treatment for intrahepatic cholangiocarcinoma (ICC) have improved patient outcomes; however, it remains a typical intractable cancer with a poor prognosis. ICC is one of the key tumors for which effective treatment may be identified through CGP testing. This study aimed to identify ICC harboring actionable genetic variants using contrast-enhanced ultrasonography (CE-US). METHODS: We enrolled 26 ICC patients who underwent CE-US before chemotherapy or surgery. Three ultrasound specialists reviewed the images by consensus and assessed the imaging features, including vascularity. Pathological data were reviewed after diagnosis using CE-US. We retrospectively analyzed distinctive CE-US findings in patients with ICC with actionable genetic variants. RESULTS: Twelve ICC patients had actionable gene variants, including four FGFR2 fusions, one FGFR2 rearrangement, six IDH1 mutations, and one BRAF V600E mutation. Univariate analysis showed significant differences in bile duct invasion (p = 0.0217) and blood vessel penetration within the tumor (p = 0.0012). Multivariable logistic regression identified blood vessel penetration within the tumor (OR = 18.275; 95% CI: 1.331-250.925; p = 0.0297) as independently associated with actionable gene variants. CONCLUSION: Patients with ICC and blood vessel penetration on CE-US should be considered for CGP testing.

Background/Objective: Ovarian cancer (OC) is one of the most lethal gynecological cancers, having a worldwide mortality rate of 66% in 2020. The overall 5-year relative survival rate is only 21% for distant stages, due to the lack of early diagnosis. Epithelial OC, the most common high-grade serous carcinoma, carries p53 mutations in most cases. However, we found that the immediate early response 5 gene (IER5), a p53 target gene, is overexpressed in ovarian cancer cells. The molecular mechanism underlying the role of IER5 in OC has not been well studied. We previously reported that IER5 promotes the dephosphorylation and activation of heat shock factor-1 (HSF1), the master regulator of proteostasis, which induces heat shock protein (HSP) expression. Methods/Results: Here we show that Ier5 mRNA expression is higher in ovarian cancer cells (MOV, ID8G, and HM-1) compared to normal ovarian cells. We also show that OC cells floating in the ascites have higher Ier5 expression than the parental strain. Knockdown of Ier5 suppressed HSP upregulation and proliferation of OC, while overexpression of IER5 promoted HSP upregulation. Knockdown of Hsf1 showed results similar to Ier5 knockdown. Conclusions: These results indicate that the IER5-HSF1 pathway contributes to the proliferation and peritoneal dissemination of OC cells. We also found that higher expression of IER5 family genes is related to poorer prognosis of OC patients, suggesting the potential of the IER5 gene family as diagnostic markers for OC, as well as potential therapeutic targets.