A Japanese family of hereditary diffuse gastric cancer with a germline pathogenic variant of CTNN1A detected via comprehensive genome profiling.

CTNNA1 codes α-1 catenin, a molecule that functions in intercellular adhesion in combination with E-cadherin (coded by CDH1). A germline pathogenic variant (GPV) of CTNNA1 increases the risk of hereditary diffuse gastric cancer (HDGC); however, this GPV has not been reported in Japan. A 35-year-old Japanese man with an advanced gastric cancer underwent comprehensive genome profiling (CGP), which led to the detection of a CTNNA1 GPV (p.

Fatal Spitz Melanoma With MAD1L1::BRAF Fusion: A Case Report and Literature Review.

Spitz melanoma is extremely rare, and only a few cases of distant metastases have been reported. Herein, we describe a case of Spitz melanoma with multiple distant metastases. A 37-year-old woman presented with a 5.

A Gene Expression Signature that Predicts Gastric Cancer Sensitivity to PARP Inhibitor Therapy.

Background/aim: Biomarkers indicating sensitivity to poly ADP-ribose polymerase (PARP) inhibitors have not yet been identified in gastric cancer. PARP inhibitors target homologous recombination deficiency (HRD); however, homologous recombination (HR) induces complex changes in gene expression, which makes it difficult to identify reliable biomarkers. In this study, we identified a multi-gene expression signature as a marker of PARP inhibitor sensitivity in gastric cancer.

Biphenotypic sinonasal sarcoma diagnosed by detection of fusion gene using integrated whole-genome and transcriptome sequencing.

Biphenotypic sinonasal sarcoma (BSNS) is a double-phenotype sarcoma that shows differentiation in both the nervous and muscular systems. To date, whole-genome and transcriptome sequencing (WGTS) has not been used to analyze BSNS. We report a patient with BSNS who was diagnosed based on rearrangement using WGTS.

Functionality-type and chemical-composition separation of poly(lactide-co-glycolide) using gradient elution normal-phase liquid chromatography with basic and acidic additives.

End groups of poly(Lactide-co-glycolide) (PLGA) play an important role in determining the properties of polymers for use in drug delivery systems. For instance, it has been reported that the encapsulation efficiency in PLGA microspheres varies significantly between ester-terminated and acid-terminated PLGA. More importantly, the in-vivo degradation time of such polymer excipients is influenced by the functional end-group of the copolymer used.

Two Japanese families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A: a case report.

Background: Germline mutations in CDKN2A result in Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) (OMIM #155,601), which is associated with an increased risk of pancreatic ductal adenocarcinoma and melanoma. FAMMM has been reported globally, but it is quite rare in Japan. We report two families with familial pancreatic cancer with suspected pathogenic variants of CDKN2A that were incidentally identified through comprehensive genomic profiling.

Headache-Related Characteristics of Biopsy-Confirmed Giant Cell Arteritis and the Relationship of Transmural Inflammation With Artery Tenderness and Chordal Thickening.

Introduction: Giant cell arteritis (GCA) is characterized by headaches, but few studies have examined the detailed characteristics of pathologically confirmed cases. We investigated the characteristics of GCA patients, particularly headache, and their correlation with pathological findings.

Methods: We retrospectively analyzed 26 patients (median age: 77.

Metabolic and Epigenetic Reprogramming in a Case of Nuclear Protein in Testis (NUT) Carcinoma of the Retroperitoneum.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive carcinoma, driven by genetic rearrangement of the NUT midline carcinoma family member 1 () gene on chromosome 15q14. Recently, a tight link has been suggested between genetic abnormalities and subsequent metabolic and epigenetic dysregulation to drive the progression of malignant tumors. However, it remains elusive whether such reprogramming could contribute to the pathogenesis of NUT carcinoma.

Thrombosis-related characteristics of pregnant women with antithrombin deficiency, protein C deficiency and protein S deficiency in Japan.

Background:  We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan.

Methods: We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology.

Valproic acid elevates HIF-1α-mediated CGB expression and suppresses glucose uptake in BeWo cells.

Placental dysfunction can disrupt pregnancy. However, few studies have assessed the effects of chemical-induced toxicity on placental function. Here, we examined the effects of valproic acid (VPA) as a model chemical on production of hormones and on glucose uptake in human choriocarcinoma cell line BeWo.

Prognostic significance of tumor microenvironment assessed by machine learning algorithm in surgically resected non-small cell lung cancer.

Background: A methodology to assess the immune microenvironment (IME) of non-small cell lung cancer (NSCLC) has not been established, and the prognostic impact of IME factors is not yet clear.

Aims: This study aimed to assess the IME factors and evaluate their prognostic values.

Methods And Results: We assessed CD8 tumor-infiltrating lymphocyte (TIL) density, forkhead box protein P3 (Foxp3 ) TIL density, and programmed death receptor ligand-1 (PD-L1) tumor proportion score (TPS) using a machine-learning algorithm in whole-slide imaging (WSI).

Comparative analysis of tumor content estimation methods based on simu- lated tumor samples identified their impact on somatic variant detection in cancer whole genome sequencing.

Whole genome sequencing (WGS) in cancer genomics has become widespread with recent technological innovations, and the amount and types of information obtained from WGS are increasing rapidly. Appropriate interpretation of results is becoming increasingly important in clinical applications. This study aimed to evaluate the accuracy of tumor content estimation and its impact on somatic variant detection, using 100 simulated tumor samples covering 10-100% tumor content constructed from the sequencing data of cell line models.

A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2.

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient's lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma.

Discordance of microsatellite instability and mismatch repair immunochemistry occurs depending on the cancer type.

Microsatellite instability (MSI) and deficiency of mismatch repair (dMMR) are key markers for predicting the response of immune checkpoint inhibitors (ICIs) and screening for Lynch syndrome (LS). This study examined the incidences of and factors associated with the concordance of MSI and MMR in human cancers. A total of 518 formalin-fixed cancer tissues were analyzed for MSI and MMR immunohistochemistry (IHC).

The efficacy of a machine learning algorithm for assessing tumour components as a prognostic marker of surgically resected stage IA lung adenocarcinoma.

Background: The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm.

Development of two 410-cancer-gene panel tests for solid tumors and liquid biopsy based on genome data of 5,143 Japanese cancer patients.

Next-generation sequencing (NGS) is an integral part of precision medicine, and its power for detecting comprehensive genetic alterations may contribute to treatment decisions for patients with advanced, recurrent, or metastatic cancer. An NGS oncology panel developed in the U.S.

Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system.

Objective: Since 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine.

Methods: Germline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study.

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

Background: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS).

Aim: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine.

Methods: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors.