Oral melanoma is a rare and aggressive subtype of melanoma that presents significant challenges in terms of delayed diagnosis and treatment. One promising clinical outcome is the detection of KIT gene mutations, which play a key role in tumor proliferation and resistance to therapy. The KIT gene encodes a receptor tyrosine kinase critical for cell survival and proliferation, and its mutations are associated with more aggressive tumor behavior. Detection of KIT mutations can be achieved through techniques such as tissue biopsy, next-generation sequencing (NGS), RT-PCR, and immunohistochemistry, providing comprehensive genomic profiling and insights into potential therapeutic targets. Precision therapies, including small-molecule inhibitors like imatinib and sunitinib, as well as combination therapies involving immune checkpoint inhibitors, offer personalized treatment strategies. Despite the potential, the rarity of oral melanoma limits clinical trials, and understanding resistance mechanisms remains a significant challenge for effective treatments for oral melanoma patients. This article highlights the critical role of KIT mutations in oral melanoma, offering insights into how molecular diagnostics can pave the way for personalized treatment approaches by focusing on advanced detection techniques and targeted therapies.

Chromosomal instability (CIN) is a pervasive feature of cancer and a major driver of tumor heterogeneity, evolution, and therapeutic resistance. Arising predominantly from defects in chromosome segregation, DNA repair, and mitotic fidelity, CIN promotes continuous genomic diversification within tumor cell populations, enabling adaptive responses to intrinsic and extrinsic selective pressures. While clonal chromosomal alterations reflect stabilized genomic configurations selected during tumor evolution, non-clonal interphase markers of chromosomal instability represent transient, low-frequency events that capture ongoing microevolutionary dynamics and genomic plasticity. This review provides a comprehensive synthesis of current knowledge regarding both classical and non-classical markers of CIN evaluated during interphase, including micronuclei, nucleoplasmic bridges, nuclear buds, cytoplasmic chromatin, massive chromosomal segregation errors, chromosomal fragmentation, and genomic chaos-related phenomena. We discuss the cellular mechanisms underlying their formation, their contribution to structural and numerical chromosomal alterations, and their role in shaping intratumoral heterogeneity, adaptive potential, malignancy acquisition, and cancer progression. Particular emphasis is placed on the "just-right" dual nature of CIN, which can either drive tumor aggressiveness or precipitate mitotic catastrophe and cell death, depending on its magnitude and cellular context. By integrating cytogenetic, molecular, and evolutionary perspectives, this review highlights the relevance of these non-clonal interphase cytogenetic markers as sensitive indicators of genome instability and tumor dynamics. Understanding the interplay between clonal and non-clonal chromosomal alterations may provide valuable insights for the development of prognostic tools and therapeutic strategies aimed at exploiting the vulnerabilities of genomically unstable cancers.

Defects in homologous recombination repair genes contribute to hereditary cancer susceptibility beyond BRCA1 and BRCA2, yet clinical interpretation of intermediate-penetrance genes remains challenging. We retrospectively evaluated unrelated carriers of pathogenic or likely pathogenic germline variants in RAD51C, RAD51D, and BRIP1 identified through hereditary cancer multigene panel testing in a real-world cohort of approximately 8000 individuals. Fifty-two carriers were included (RAD51C n = 14, RAD51D n = 15, BRIP1 n = 23). Ovarian cancer represented the predominant malignancy, followed by breast cancer, consistent with established gene-phenotype associations. Most detected variants were predicted loss-of-function alterations. Six previously unreported variants were identified, expanding the mutational spectrum of RAD51C and RAD51D. Recurrent variants were observed in unrelated individuals, including BRIP1 c.2992_2995del, which demonstrated higher frequency in regional population data compared with global datasets, suggesting possible population enrichment. Additional pathogenic variants in ATM and BRCA1 were identified in two individuals, highlighting the complexity of multigene testing. Although non-classical tumour types were occasionally observed, including colorectal cancer in BRIP1 carriers, causal associations remain uncertain. These findings emphasize the importance of population-aware variant interpretation and individualized genetic counseling aligned with contemporary ACMG and ESMO recommendations for moderate-penetrance hereditary cancer genes.

TP53 mutation is one of the most frequently altered genetic variants leading to hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) in this gene play a crucial role in predicting the risk of HCC development. This study aimed to analyze how SNPs in the human TP53 gene affect protein stability, structure, localization, and other physicochemical properties. The coding sequence (CDS) and SNP data of TP53 were retrieved from the Ensembl database. CDS were translated using the ExPASy Translate tool. Mutated protein sequences were analyzed using ProtParam, I-MUTANT, CELLO2, SOPMA, SWISS-MODEL, SAVES v6.0, and the HDOCK server to evaluate physicochemical properties, stability, subcellular localization, secondary and tertiary structures, structure validation, and docking behavior. Among 30 SNPs analyzed, three SNPs (rs1555526997 in exon 15, rs1567556784 in exon 59, and rs869054324 in exon 66) showed complete alterations in physicochemical properties, subcellular localization, 2D and 3D structures, and ERRAT and PROCHECK values. The study identified 21 missense, 3 frameshift, and 6 stop-gained mutations. Of the missense mutations, seven SNPs showed a decreasing effect on protein stability. This study demonstrates the effectiveness of in silico approaches in predicting HCC associated biomarkers and assessing the functional impact of TP53 mutations.

Glial tumors are the most common malignant brain tumors, and IDH1 serves as an important diagnostic and prognostic molecular marker in gliomas. The mutation status of IDH1 influences prognosis, patient survival, and treatment response in glial tumors. However, the effects of the IDH1 mutation on the angiogenic potential of glial tumors have yet to be thoroughly elucidated. Our aim was to investigate the impact of the IDH1 mutation on the angiogenic potential of glial tumors by overexpressing both mutant and wild-type IDH1 genes in these tumors. Furthermore, we examined how the signaling pathways affecting the angiogenic behavior of glial tumors differ based on IDH1 mutation status by evaluating the mRNA expressions of VEGF, EGF, PDGF, and FGF signaling pathways in the U87MG cell line as well as in patient-derived tumor samples. The IDH1 mutation induced proliferation and tube-formation potential in U87MG cells while suppressing these activities in HUVEC cells. Considering angiogenesis-associated signaling pathways, we found that mutant IDH1 expression indirectly upregulates angiogenesis-associated pathways via HIF1A. The genes VEGFC, ERBB3, PDGFB, and PDGFC may serve as potential markers for the prognosis of glial tumors and for anti-angiogenic therapy.

Esophageal cancer (ESCA) ranks among the most lethal malignancies worldwide, with late-stage diagnosis, poor prognosis, and limited treatment options contributing to its high mortality. MicroRNAs (miRNAs), short non-coding RNAs with gene-silencing functions, have emerged as crucial regulators in cancer biology and hold promise as diagnostic and therapeutic tools. This study investigates miRNA-mRNA interactions in ESCA using a comprehensive in silico approach to uncover potential regulatory nodes that may underlie tumor progression. Fourteen overexpressed genes in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) were selected. TargetScanHuman and miRDB were used to detect miRNAs with high-confidence 8mer seed matches (score ≥90). The majority of genes exhibited multi-miRNA targeting with clustered or overlapping seed regions, indicative of cooperative or redundant repression mechanisms. Several miRNAs demonstrated highly stable interactions, with favorable MFE and ΔG values, reinforcing their silencing potential. GC/GC3 enrichment further supported duplex stability. GO analysis revealed that the target genes are predominantly involved in transcriptional regulation, apoptosis inhibition, immune response modulation, and cell signaling-pathways central to cancer pathogenesis. TCGA-based validation showed that only a subset of predicted interactions is functionally relevant, with hsa-miR-30d-5p exhibiting a significant inverse correlation with CHST2. These findings highlight the importance of integrating predictive and expression data to identify biologically meaningful miRNA-mRNA interactions in esophageal cancer.

The polymerase chain reaction (PCR) is a fundamental technique in molecular biology, enabling the amplification of specific DNA sequences for various applications. Despite its utility, the fidelity of DNA polymerases used during amplification is not perfect, leading to the introduction of replication errors such as base substitutions, insertions, and deletions into the amplified products. These errors can significantly impact downstream analyses, where correct identification of true biological DNA variations is crucial. This study aimed to investigate the error rates of Taq polymerase during PCR amplification of a 127 base pair sequence surrounding codon 600 of the BRAF gene. This region, located in exon 15, is of significant clinical interest due to its association with various cancers. Using the MiSeq platform in combination with a constant denaturant capillary electrophoresis (CDCE) assay, we analyzed the errors introduced by Taq polymerase. On average, 1.1 million sequencing reads were generated for each PCR-amplified sample, in combination with mutant enrichment through CDCE to allow for the observation of mutations from the background noise. We identified a non-random mutational spectrum with respect to positions, with several hotspots. The majority of mutational changes were transitions, either A to G or T to C. Noteworthy is the mutation in codon 600, where the second base "T" is mutated to an "A," corresponding to the clinically relevant V600E mutation. This study highlights the importance of understanding polymerase-induced errors in PCR and their implications for NGS data accuracy. The enrichment strategy employed here demonstrates a method for detecting and analyzing these errors, providing valuable insights for genomic research and clinical applications.

Early metabolic events during the intrauterine period can increase susceptibility to chronic diseases in adulthood. Fetal and neonatal nutrition rich in sugars may lead to disorders such as obesity, insulin resistance, and diabetes. This study evaluated the effects of maltodextrin and sucrose intake in Swiss female mice treated during gestation and lactation, as well as in their offspring. Sixty-day-old mating pairs were used, receiving nutritional interventions (maltodextrin 10%/L, sucrose 10%/L, or water) during mating, gestation, and lactation (7, 21, and 21 days, respectively), totaling 49 days. Genetic (comet assay, micronucleus test) and biochemical (glycemia and electron transport chain) analyses were performed in dams and in offspring of both sexes at postnatal days (PND) 21 and 30. In dams, food intake and body weight were monitored, whereas in offspring, anthropometric parameters were assessed. Results showed that both carbohydrates increased fluid and calorie intake without affecting maternal body weight. Sucrose raised fasting glucose significantly. Comet assay revealed increased DNA damage after gestation and lactation, especially in the cortex for maltodextrin (p < 0.05), with no changes in liver or hippocampus. The micronucleus test showed increased PCE micronuclei in the maltodextrin group (p < 0.05). Complex I activity increased in the liver with both carbohydrates, while Complex II-III decreased with sucrose. In the cortex, both carbohydrates increased Complex II and reduced Complex IV; in the hippocampus, Complex I increased with both, and Complex IV increased with maltodextrin. In the offspring, sucrose-exposed males had greater body weight at 21 days, and females showed increased glycemia at 30 days. Overall, findings suggest that maltodextrin and sucrose intake during pregnancy and lactation can induce long-term metabolic and genetic alterations in mothers and offspring.