Case-Control Study for 23 Cancer Types With Functional Analysis of : Risk Estimation and Clinical Recommendations in East Asia.

Purpose: is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clinical relevance of germline variants differs across population, there is little evidence of the clinical relevance of germline variants in East Asia.

Prediction recurrence in stage I epidermal growth factor receptor-mutated non-small cell lung cancer using multi-modal data.

Introduction: Integrated recurrence prediction models that combine clinical, imaging, and genetic data are lacking for epidermal growth factor receptor (EGFR)-mutated stage I non-small cell lung cancer (NSCLC). We developed a recurrence prediction model for Stage I EGFR-mutated NSCLC by integrating clinical, radiological, and whole-exome sequencing (WES) data.

Methods: A total of 306 patients with Stage I EGFR-mutated NSCLC were stratified into training (n = 206) and validation (n = 100) cohorts using stratified random sampling.

Clarification of the clinical significance of an intron variant in a case of Peutz-Jeghers syndrome with abnormal RNA splicing of STK11.

Unlabelled: Peutz–Jeghers syndrome is an autosomal dominant disease characterized by intestinal polyposis, mucocutaneous pigmentation, and an increased risk of various types of cancer. Germline mutations in (), which encodes serine/threonine kinase 11, have been identified as the major cause of Peutz–Jeghers syndrome. Here, we detected a rare variant of undetermined significance in intron 2 of using multi-gene panel analysis in a girl with clinically suspected Peutz–Jeghers syndrome.

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

Human papillomavirus (HPV) infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix (GAS), a rare aggressive subtype without HPV infection. To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of GAS and usual-type endocervical adenocarcinoma (UEA) in three independent cohorts of patients with GAS and UEA. The first cohort comprised eight GAS and 22 UEA patients treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing.

Comparison between a Luminex-based multiplex kit with a sequence-specific oligonucleotide probe and next-generation sequencing for the detection of POLE oncogenic mutations in endometrial cancer.

In endometrial cancer, detection of oncogenic mutations in the polymerase epsilon (POLE) gene is crucial for accurate staging according to the 2023 International Federation of Gynecology and Obstetrics classification and for minimizing overtreatment. However, POLE sequencing is expensive, time-consuming, and often inaccessible in settings without specialized equipment. We developed a novel multiplex kit for the detection of POLE mutations using a Luminex (xMAP) assay in a single reaction.

Favorable response to nivolumab combined with radiotherapy for retroperitoneal leiomyosarcoma.

Unlabelled: Retroperitoneal sarcoma (RPS) is a biologically heterogeneous tumor and rare malignant mesenchymal soft-tissue neoplasm. Although the 5-year overall survival rate for RPS is approximately 60%-70%, it is quite low for unresectable tumors. Surgery is a standard treatment for RPS.

Genomic Profiles of Pathogenic and Moderate-Penetrance Germline Variants Associated With Risk of Early-Onset Lung Adenocarcinoma.

Introduction: Up to 54% of all lung adenocarcinoma (LADC) cases in Asian populations occur in never-smoking women, suggesting that the impact of smoking and other environmental factors on the risk of early-onset LADC is minimal. Genetic factors may play a crucial role in disease development.

Methods: The prevalence of germline pathogenic variants (GPVs) of 454 hereditary cancer and DNA repair genes was evaluated by whole-exome and whole-genome sequencing of 348 early-onset LADC (aged ≤ 40 y) and 1425 later-onset LADC (aged ≥ 41 y) cases.

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

Background: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear.

Patients And Methods: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD.

Germline Pathogenic Variants and Clinical Outcomes in Asian Patients With Breast Cancer.

Despite the importance of genetic testing for risk assessment and treatment in breast cancer, the prognostic impact of germline pathogenic variants (PVs), especially in Asian populations, is unclear. We assessed the impact of germline PVs in patients with early-stage breast cancer. This study included 7278 Japanese multihospital registry patients.

TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases.

Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with ∼30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components.

Cancer and disease profiles for PTEN pathogenic variants in Japanese population.

A germline alteration in the PTEN gene causes a spectrum of disorders conceptualized as PTEN hamartoma tumor syndrome (PHTS), which show high risk of tumor development and a highly variable and complex phenotype. The diagnosis of PHTS is established in a proband by identification of a heterozygous germline PTEN pathogenic variant on molecular genetic testing. In this study, to understand more PTEN-associated clinical phenotype and PHTS in a Japanese population, we extracted 128 germline PTEN rare variants from 113,535 adult Japanese registered in Biobank Japan (BBJ), and categorized 29 pathogenic/likely pathogenic variants in 30 individuals (0.

Clinicopathological and molecular features of claudin-18 isoform 2 expression in patients with colorectal cancer: a single-center retrospective study.

Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.

Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database.

Purpose: Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined.

Multi-omics and clustering analyses reveal the mechanisms underlying unmet needs for patients with lung adenocarcinoma and identify potential therapeutic targets.

Background: The cancer genome contains several driver mutations. However, in some cases, no known drivers have been identified; these remaining areas of unmet needs, leading to limited progress in cancer therapy. Whole-genome sequencing (WGS) can identify non-coding alterations associated with the disease.

Oncofetal IGF2BP3-mediated control of microRNA structural diversity in the malignancy of early-stage lung adenocarcinoma.

The nature of microRNA (miRNA) dysfunction in carcinogenesis remains controversial because of the complex connection between miRNA structural diversity and biological processes. Here, we found that oncofetal IGF2BP3 regulates the selective production of a subset of 3'-isoforms (3'-isomiRs), including miR-21-5p and Let-7 family, which induces significant changes in their cellular seed occupancy and structural components, establishing a cancer-specific gene expression profile. The D-score, reflecting dominant production of a representative miR-21-5p+C (a 3'-isomiR), discriminated between clinical early-stage lung adenocarcinoma (LUAD) cases with low and high recurrence risks, and was associated with molecular features of cell cycle progression, epithelial-mesenchymal transition pressure, and immune evasion.

Excellent concordance of the molecular classification between preoperative biopsy and final hysterectomy in endometrial carcinoma.

Objective: The 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging.

Dietary vitamin D intake and risk of colorectal cancer according to vitamin D receptor expression in tumors and their surrounding stroma.

Background: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC.

Methods: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry.

Mechanism of ERBB2 gene overexpression by the formation of super-enhancer with genomic structural abnormalities in lung adenocarcinoma without clinically actionable genetic alterations.

Background: In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants are frequently identified in several hundred loci per case.

Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.

Objective: The efficacy of pembrolizumab in patients with microsatellite instability (MSI)-high cancers has been reported; however, the differences in efficacy according to the subtypes of MSI-high endometrial cancers (ECs) remain unclear. MSI-high ECs are classified into at least 3 groups based on their molecular characteristics: hypermethylated, Lynch-like syndrome (LLS)-associated, and Lynch syndrome (LS)-associated cancers. This study aimed to investigate whether the efficacy of pembrolizumab differs among these 3 groups, and if so, whether EPM2AIP1 immunohistochemistry (IHC), which correlates with promoter methylation, can be used to rule out methylation cases.

Rapid Response to Lenvatinib and Disease Flare After Discontinuation in a Patient With Thymic Carcinoma Harboring KIT Exon 11 Mutation: A Case Report.

Lenvatinib, a multitarget tyrosine kinase inhibitor for c-Kit and other kinases, has exhibited promising efficacy in treating advanced or metastatic thymic carcinoma (TC). Here, we present the case of a patient with metastatic TC harboring a exon 11 deletion and amplification. The patient exhibited a remarkable response to lenvatinib but experienced rapid disease progression after discontinuation of lenvatinib, referred to as a "disease flare.