RNA sensing induced by chromosome missegregation augments anti-tumor immunity.

Viral mimicry driven by endogenous double-stranded RNA (dsRNA) stimulates innate and adaptive immune responses. However, the mechanisms that regulate dsRNA-forming transcripts during cancer therapy remain unclear. Here, we demonstrate that dsRNA is significantly accumulated in cancer cells following pharmacologic induction of micronuclei, stimulating mitochondrial antiviral signaling (MAVS)-mediated dsRNA sensing in conjunction with the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene.

ETV6::LYN fusion gene is recognized as one of the genetic alterations responsible for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) according to the 2022 WHO classification. However, the clinical features and pathogenesis of MLN-TK with ETV6::LYN are not well defined because of the rarity of the disease. Here, we report an MLN-TK patient with ETV6::LYN that manifested as myeloproliferative neoplasms (MPN) with eosinophilia, myelofibrosis, and T-lymphoblastic lymphoma (T-LBL), which eventually led to acute myeloid leukemia.

Age-related genomic alterations and chemotherapy sensitivity in osteosarcoma: insights from cancer genome profiling analyses.

Background: Osteosarcoma, the most common primary bone malignancy, has a complex genetic basis and two incidence peaks. In younger patients, the standard treatment involves wide surgical resection combined with adjuvant chemotherapy; however, the role of chemotherapy in elderly patients remains controversial. The aims of this study were to investigate genetic differences between younger and elderly patients with osteosarcoma and to identify genetic signatures associated with chemotherapy response.

combined with L858R mutation reduced afatinib sensitivity and associated to early recurrence in lung cancer.

Background: The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for -mutated non-small cell lung cancer (NSCLC). However, there is no established treatment for osimertinib resistance, so second-generation afatinib is an alternative treatment option. The purpose of this study was to elucidate gene alterations associated with afatinib efficacy and resistance by analyzing cell-free DNA (cfDNA) obtained from patients with -mutated NSCLC.

Post-transplant transient abnormal myelopoiesis evolving from a GATA1 mutant clone in umbilical cord blood.

Transient abnormal myelopoiesis (TAM) generally affects newborns with Down syndrome and is associated with constitutional trisomy 21 and a somatic GATA1 mutation. Here we describe a case of TAM which evolved after umbilical cord blood transplantation (UCBT), whose origin was identified as a GATA1 mutation-harboring clone in umbilical cord blood (UCB) by detailed genetic analyses. A 58-year-old male who received UCBT for peripheral T-cell lymphoma presented progressive anemia and thrombocytopenia, and leukocytosis with blast cells in the peripheral blood (PB).

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.

Primary large B-cell lymphoma of the central nervous system: A reappraisal of CD5-positive cases based on clinical, pathological, and molecular evaluation.

CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive () PCNS-LBCL cases, occupying 6.

Early progressive disease within 2 years in isocitrate dehydrogenase (IDH)-mutant astrocytoma may indicate radiation necrosis.

Background: Isocitrate dehydrogenase-mutant astrocytoma without cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion typically follows a slow clinical course. However, some cases show early progression on magnetic resonance imaging, and these characteristics remain under-reported. This study aimed to elucidate the characteristics of isocitrate dehydrogenase-mutant astrocytoma showing early progression on magnetic resonance imaging.

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.

Establishment and characterization of NCC-GCTB10-C1: a novel cell line derived from a patient with recurrent giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a rare osteolytic tumor composed of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. While generally benign, GCTB has a high risk of local recurrence and can occasionally undergo malignant transformation or metastasis, posing significant clinical challenges. The primary treatment is complete surgical resection; however, effective management strategies for recurrent or advanced GCTB remain elusive, underscoring the need for further preclinical research.

Establishment and characterization of a novel patient-derived cell line from conventional central grade 3 chondrosarcoma, NCC-CS1-C1.

Chondrosarcoma (CS) is a malignant tumor that produces cartilaginous matrix and is the second most common primary bone sarcoma. CS encompasses a range of histological subtypes, with high-grade conventional central CS being particularly rare, occurring at a rate of 1.81 cases per 1 million person-years.

Clonal hematopoiesis in cancer predisposition syndromes.

After recent advances in sequencing technologies led to the discovery of novel genes associated with predisposition to hematological malignancies, studies have now shown that myeloid neoplasms associated with germline variants are more common than previously estimated. Based on these findings, myeloid neoplasms with germline predisposition have emerged as a unique category in the recent World Health Organization classification of Haematolymphoid Tumors. Clonal hematopoiesis is common in healthy individuals, particularly in older people.

Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development.

The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses.

Efficacy of CBP/p300 Dual Inhibitors against De-repression of KREMEN2 in cBAF-Deficient Cancers.

The SWI/SNF chromatin remodeling complex is divided into three subcomplexes: cBAF, PBAF, and ncBAF. Constituent genes (e.g.

The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment.

Regulatory T (Treg) cells play key roles in cancer immunity by suppressing a range of antitumor immune responses and contributing to resistance to programmed death (PD)-1 blockade therapy. Given their critical roles in self-tolerance, local control of immunosuppression by Treg cells, such as in the tumor microenvironment (TME), has been intensively studied. Inhibition of heat shock protein 90 (HSP90), a chaperone with vital roles in regulating proteostasis in cancer cells, impedes cancer progression by interrupting oncogenic signaling pathways and potentially modulating antitumor immunity, but we have very little mechanistic insight into these immune modulatory effects.

Introduction of AI Technology for Objective Physical Function Assessment.

Objective physical function assessment is crucial for determining patient eligibility for treatment and adjusting the treatment intensity. Existing assessments, such as performance status, are not well standardized, despite their frequent use in daily clinical practice. This paper explored how artificial intelligence (AI) could predict physical function scores from various patient data sources and reviewed methods to measure objective physical function using this technology.

Early separation and parallel clonal selection of dedifferentiated and well-differentiated components in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma (DDLPS) comprises a high-grade dedifferentiated (DD) component and a juxtaposed well-differentiated (WD) component. The DD component is believed to originate from the WD component by acquiring additional genomic alterations. In this study, we performed multiregion genome, epigenome, and transcriptome analyses of three patients with DDLPS.

Circulating serum miRNAs predict response to platinum chemotherapy in high-grade serous ovarian cancer.

Background: Platinum chemotherapy is the cornerstone of treatment for high-grade serous ovarian cancer (HGSOC); however, validated biomarkers that can accurately predict platinum response are lacking. Based on their roles in the underlying pathophysiology, circulating microRNAs are potential, noninvasive biomarkers in cancer. In the present study, we aimed to evaluate the circulating miRNA profiles of patients with HGSOC and to assess their potential utility as biomarkers to predict platinum response.