Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 8, 2025

The study was designed to evaluate molecular alterations, relevant the prognosis and personalized therapy of salivary gland cancers (SGCs). DNA extracted from archival tissue 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel used for identification small-scale mutations, focal chromosomal arm-level copy number changes. final analysis included selected genes potential actionable aberrations therapies outcome predictions in 37 tumours' samples. follow-up cohort revealed disease recurrence or metastasis 19 indicated poor individual outcomes. mean disease-free survival (DFS) within group 2.4 years, overall (OS) 5.4 years. DFS OS remaining 18 favourable outcomes were 8.3 most frequently affected NF1 (n = 9, 24%) TP53 8, 22%), increased occurrence observed group: 6, 32%) 32%). CDKN2A biallelic deletion common variation 5), detected 4 cases identified relapse. TERT promoter mutation amplification found myoepithelial carcinoma. p.Ile35Thr discovered CTNNB1 two adenoid cystic ERBB2 alterations remarkable SDC ex PA. Furthermore, established as a negative prognostic factor (p 0,04). potentially in: MECA 100% (1/1), (7/7), AD 92% (11/12), Ca PA 82% (18/22), 65% (20/31), AdCC 64% (9/14) AcCC 0% (0/1). are heterogeneous malignancies distinct landscape that characterized by inadequate treatment options. Nonstandard strategies might be beneficial who suffer cancers. Wider utilization NGS may increase opportunity those rare receive more precise, therapy.

Language: Английский

---

Recent progress in emerging molecular targeted therapies for intrahepatic cholangiocarcinoma

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Small-molecule and antibody-based targeted therapies for intrahepatic cholangiocarcinoma (iCCA): addressing promising oncogenic molecular alterations, including IDH1, FGFR2, BRAF, HER2, the PD-1/PD-L1 axis.

Language: Английский

---

Integrative Analysis of Gene Expression and Promoter Methylation to Differentiate High-Grade Serous Ovarian Cancer from Benign Tumors

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 441 - 441

Published: Feb. 11, 2025

Background: Ovarian cancer (OC) is the third most common and second lethal onco-gynecological disease in world, with high-grade serous ovarian (HGSOC) making up majority of OC cases worldwide. The current serological biomarkers used for diagnosis are lacking sensitivity specificity, thus new greatly needed. Recently, chromatin remodeling complex gene ARID1A, Notch Wnt pathway expression, as well HOX-related promoter methylation have been linked promoting OC. Methods: In this pilot study, 10 expression 4 were examined potential diagnostic prognostic indicators 65 fresh-frozen gynecologic tumor tissues. Results: Out genes analyzed, eight was significantly reduced compared to benign, increased tumors. 14 biomarkers, CTNNB1 showed best single biomarker separation HGSOC from benign (AUC = 0.97), while a combination seven pathway-related expressions (NOTCH1, NOTCH2, NOTCH3, NOTCH4, DLL1, JAG2, HES1) demonstrated 1). Conclusions: multiple or shows great promise development an effective biomarker-based approach

Language: Английский

---

The Histomorphology to Molecular Transition: Exploring the Genomic Landscape of Poorly Differentiated Epithelial Endometrial Cancers

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 382 - 382

Published: March 5, 2025

The peremptory need to circumvent challenges associated with poorly differentiated epithelial endometrial cancers (PDEECs), also known as Type II (ECs), has prompted therapeutic interrogation of the prototypically intractable and most prevalent gynecological malignancy. PDEECs account for cancer-related mortalities due their aggressive nature, late-stage detection, poor response standard therapies. are characterized by heterogeneous histopathological features distinct molecular profiles, they pose significant clinical propensity rapid progression. Regardless complexities around PDEECs, still being administered inefficiently in same manner clinically indolent readily curable type-I ECs. Currently, there no targeted therapies treatment PDEECs. realization new options transformed our understanding enabling more precise classification based on genomic profiling. transition from a provided critical insights into underlying genetic epigenetic alterations these malignancies. This review explores landscape focus identifying key subtypes mutations that variants. Here, we discuss how correlates outcomes can refine diagnostic accuracy, predict patient prognosis, inform strategies. Deciphering underpinnings led advances precision oncology protracted remissions patients untamable

Language: Английский

---

Multidimensional OMICs reveal ARID1A orchestrated control of DNA damage, splicing, and cell cycle in normal‐like and malignant urothelial cells

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

---

Identification of MEF2A, MEF2C, and MEF2D interactomes in basal and Fsk‐stimulated mouse MA‐10 Leydig cells

Andrology, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Background Myocyte enhancer factor 2 transcription factors regulate essential transcriptional programs in various cell types. The activity of myocyte is modulated through interactions with cofactors, chromatin remodelers, and other regulatory proteins, which are dependent on context physiological state. In steroidogenic Leydig cells, MEF2A, MEF2C, MEF2D key regulators genes involved steroid hormone synthesis, reproductive function, oxidative stress defense. However, the specific network 2‐interacting proteins cells remains unknown. Objective To identify interactome each MEF2 present cells. Materials methods TurboID proximity‐mediated biotinylation combined mass spectrometry bioinformatic analyses were used to protein‒protein interaction networks MA‐10 under basal stimulated conditions. Results We identified 109 potential including some previously known partners. for dynamic exhibits unique shared between Further analysis Gene Ontology Kyoto Encyclopedia Genes Genomes pathway enrichment categorized these interactions, revealing involvement pathways related cellular metabolism, regulation, steroidogenesis. Discussion conclusion These findings suggest that can participate diverse activities, capable gene activation or repression, depending different interactions. addition, differential suggests roles modulating function. Overall, this study provides new mechanistic insights into action by identifying interacting partners likely influence their functions.

Language: Английский

---

Molecular biomarkers of progression in non-muscle-invasive bladder cancer — beyond conventional risk stratification

Nature Reviews Urology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

Language: Английский

---

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database

Japanese Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 53(9), P. 798 - 807

Published: June 24, 2023

Abstract Background Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis large cohorts with next-generation sequencing by histologic type has not been adequately performed. Methods We analysed data from 93 patients duct carcinoma and 243 adenoid cystic who underwent comprehensive profiling testing Center for Cancer Genomics Advanced Therapeutics database, a Japanese national genome database. visualised gene mutation profiles using OncoPrinter platform. Fisher’s exact test, Kaplan–Meier analysis, log-rank test Cox regression models were used statistical analysis. Results In population CDK12 ERBB2 co-amplification was detected 20 37 (54.1%) amplification. identified five loss-of-function variants genes related homologous recombination deficiency, such as BRCA2 CDK12. survival showed that is associated overall (hazard ratio, 3.597; P = 0.045). NOTCH1 mutations most common, followed chromatin modification KMT2D, BCOR, KDM6A, ARID1A, EP300 CREBBP. multivariate activating 3.569; 0.009) ARID1A 4.029; 0.034) significantly survival. Conclusion poor prognosis carcinoma. Chromatin remodelling are deeply involved tumour progression One gene, an independent prognostic factor. there might be minor populations could targeted treatment synthetic lethality approach.

Language: Английский

---

Multi-scale characterisation of homologous recombination deficiency in breast cancer

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Nov. 2, 2023

Homologous recombination is a robust, broadly error-free mechanism of double-strand break repair, and deficiencies lead to PARP inhibitor sensitivity. Patients displaying homologous deficiency can be identified using 'mutational signatures'. However, these patterns are difficult reliably infer from exome sequencing. Additionally, as mutational signatures historical record mutagenic processes, this limits their utility in describing the current status tumour.

Language: Английский

---

Dysregulation of SWI/SNF Chromatin Remodelers in NSCLC: Its Influence on Cancer Therapies including Immunotherapy

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 984 - 984

Published: June 13, 2023

Lung cancer is the leading cause of death worldwide. Molecularly targeted therapeutics and immunotherapy revolutionized clinical care NSCLC patients. However, not all patients harbor molecular targets (e.g., mutated EGFR), only a subset benefits from immunotherapy. Moreover, we are lacking reliable biomarkers for immunotherapy, although PD-L1 expression has been mainly used guiding front-line therapeutic options. Alterations SWI/SNF chromatin remodeler occur commonly in with NSCLC. This tumors tends to be undifferentiated presents high heterogeneity histology, it shows dismal prognosis because poor response current standard therapies. Catalytic subunits SMARCA4/A2 DNA binding ARID1A/ARID1B/ARID2 as well PBRM1 were identified most complexes Mechanistically, alteration these contributes tumorigenesis through compromising function critical tumor suppressor genes, enhancing oncogenic activity impaired repair capacity related genomic instability. Several vulnerabilities NSCLCS altered detected evaluated clinically using EZH2 inhibitors, PROTACs mutual synthetic lethal paralogs PARP inhibitors. The an ICIs might confounded by coexistence mutations genes capable influencing patients’ ICIs. High heterogenicity deficiency also responsible seemingly conflicting results ICI treatment alterations SWI/SNF. In addition, each different subunit have unique impact on deficient subunits. Prospective studies required evaluate how treatment. Finally, worthwhile point out that combining inhibitors other modulators proven effective remodelers.

Language: Английский

---