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Metastatic colorectal cancer (mCRC) presents notable therapeutic challenges. Rat sarcoma virus () mutations, including those in exon 2, are critical for treatment decisions; however, the role of minor mutations ( exons 3 and 4, and ) remains underexplored. Because these mutations are increasingly identified in routine practice due to advances in mutation testing that now routinely includes exons 3 and 4, and , clarifying their clinical relevance has become important for ensuring appropriate treatment selection. The present study aimed to compare the clinical and prognostic characteristics of patients with mCRC with minor mutations to those with exon 2 mutations. To this end, data were retrospectively collected from patients with mCRC and mutations between August 2018 and December 2023. Patients were grouped based on mutation subtype: exon 2 or minor mutations. mutation testing was performed using the MEBGEN RASKET™-B kit. Clinical characteristics, tumor location, metastatic patterns and survival outcomes were analyzed. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazards regression models. Of 202 patients with mutations, 170 had exon 2 mutations, whereas 32 exhibited minor mutations (20 with non-exon 2 mutations and 12 with mutations). Minor mutations were more common in left-sided CRC. No significant differences in background were observed between the two groups. Log-rank OS was comparable for patients with exon 2 and minor mutations. OS and PFS with first-line bevacizumab-containing therapy were also similar between the two groups. In conclusion, the prognostic impact of minor mutations appears to be comparable to that of exon 2 mutations, suggesting that the current treatment strategies for -mutant CRC may not require modification based on these findings.
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http://dx.doi.org/10.3892/ol.2025.15123 | DOI Listing |
Anal Methods
September 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Avapritinib (Ayvakit™) is a highly selective inhibitor of the platelet-derived growth factor receptor alpha (PDGFRA), including D842V mutations. Avapritinib (APB) is authorized in the United States for individuals with metastatic or unresectable gastrointestinal stromal tumors (GISTs). APB is considered the exclusive therapy for adults with indolent systemic mastocytosis.
View Article and Find Full Text PDFProteomics Clin Appl
September 2025
AIBioMed Research Group, Taipei Medical University, Taipei, Taiwan.
Background: Endometrial carcinoma (EC) represents a significant clinical challenge due to its pronounced molecular heterogeneity, directly influencing prognosis and therapeutic responses. Accurate classification of molecular subtypes (CNV-high, CNV-low, MSI-H, POLE) and precise tumor mutational burden (TMB) assessment is crucial for guiding personalized therapeutic interventions. Integrating proteomics data with advanced machine learning (ML) techniques offers a promising strategy for achieving precise, clinically actionable classification and biomarker discovery in EC.
View Article and Find Full Text PDFMol Cell Neurosci
September 2025
Department of Personalized & Molecular Medicine, Era University, Lucknow, India.
Epilepsy is a neurological disorder that shows strong genetic control on the timing and onset of symptoms and drug response variability. Some epilepsy syndromes have clear monogenic mutations but genes with control on the phenotype and severity of the disorder and drug sensitivity are present in the whole genetic profile. Genetic modifiers are not the cause of epilepsy but control significant networks such as synaptic plasticity and ion channels and neurodevelopment and neuroinflammation and therefore the reason why two individuals with the same primary mutations have different clinical courses.
View Article and Find Full Text PDFIntroduction: The Clinical Genome Resource (ClinGen) Von Hippel-Lindau (VHL) Variant Curation Expert Panel (VCEP) has created variant classification specifications tailored to the gene, including phenotype-driven and evidence-based criteria, somatic and germline mutational hotspots, functional and in-silico data.
Materials And Methods: Using the American College of Medical Genetics and Genomics (ACMG) guidance and the ClinGen Sequence Variant Interpretation (SVI) recommendations, the VCEP made substantial modifications to eight evidence codes (PVS1, PS3, PS4, PM1, BS2, BS3, BS4, BP5), while 14 had minor or no changes and 6 were not used (PM3, PP2, BP1, PP4, PP5/BP6). The VHL VCEP applied two literature sets of over >428 papers in Clinical Interpretations of Variants in Cancer (CIViC) and >8700 structured annotations using Hypothesis.
Head Neck Pathol
September 2025
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Purpose: Sialoblastoma is an extremely rare low-grade malignant salivary gland neoplasm that presents at birth or early infancy and has heterogeneous clinical behavior. Due to its rarity, the molecular landscape remains incompletely characterized. We aimed to expand the current understanding of the genetic alterations in sialoblastoma through comprehensive molecular analysis.
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