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Background: This study was to determine the prevalence and clinical significance of clonal hematopoiesis (CH)-related variants, and somatic and germline mutations in cancer patients and healthy individuals. Methods: We performed next-generation sequencing of 275 cancer-related genes be-tween plasma and white blood cells in 92 cancer patients and 47 controls without cancer. Blood samples were recruited from May 2017 to July 2021, and blood cancer patients were excluded. For all statistical analysis in this study, p < 0.05 was considered statistically significant. Results: Overall, 38.04% of patients and 46.81% of controls harbored at least one CH-related mutation in plasma cell-free DNA. Based on our results, older cancer patients exhibited a CH phenomenon more frequently than younger patients (p = 0.0024). A total of 39 somatic pathogenic (P)/likely pathogenic (LP) mutations were identified in 17 genes in 21 of 92 patients. We found that the presence of P/LP variants in cancer-related gene predicted shorter overall survival (OS) (p = 0.001). Multivariate analysis adjusted for CH-related mutations, germline mutations, and tumor stage, also indicated that somatic mutations correlated significantly with OS (p = 0.022). Moreover, the frequency of a germline P/LP variant was that of seven of 92 individuals in the cancer group and one of 42 individuals in the control group. Conclusions: We characterized the CH-related variants, and somatic and germline mutations in cancer patients and healthy individuals, and the results have important clinical significance. [ABSTRACT FROM AUTHOR]

Head and neck cancer has poor overall survival. Patients with head and neck cancer more frequently develop second primary tumors than do patients with other cancers, leading to a poor prognosis. In this study, we used next-generation sequencing to analyze and compare mutations between first tumors and second tumors in oral cancer. We retrieved tumor tissues collected from 13 patients who were diagnosed twice as having cancer. We used driver gene and trunk mutations to distinguish between recurrent cancer and primary cancer in oral cancer. We observed unique driver gene mutations in three patients with an initial clinical diagnosis of recurrent cancer; hence, we believe that the corresponding patients had primary cancer. Four patients with an initial clinical diagnosis of primary cancer were found to actually have recurrent cancer according to our results. Genetic testing can be used to enhance the accuracy of clinical diagnosis. [ABSTRACT FROM AUTHOR]

This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS. [ABSTRACT FROM AUTHOR]

Simple Summary: Human cancer genomes show a variety of alterations, such as single base changes, deletions, insertions, copy number changes, and gene fusions. Analyzing fusion gene transcripts may yield a novel and effective approach for selecting cancer treatments. However, few comprehensive analyses of gene fusions in non-small cell lung cancer (NSCLC) patients have been performed. Here, we characterized the fusion gene landscape of NSCLC in a case study of Taiwanese lung cancer patients. We concluded that some fusion genes likely play driver roles in carcinogenesis, while others act as passengers. We demonstrated that by using RNA-sequencing to detect gene fusion events, putative therapeutic drug targets could be identified, potentially leading to more precise therapies for NSCLC. Background: Analyzing fusion gene transcripts may yield an effective approach for selecting cancer treatments. However, few comprehensive analyses of fusions in non-small cell lung cancer (NSCLC) patients have been performed. Methods: We enrolled 54 patients with NSCLC, and performed RNA-sequencing (RNA-Seq). STAR (Spliced Transcripts Alignment to a Reference)-Fusion was used to identify fusions. Results: Of the 218 fusions discovered, 24 had been reported and the rest were novel. Three fusions had the highest occurrence rates. After integrating our gene expression and fusion data, we found that samples harboring fusions containing ASXL1, CACNA1A, EEF1A1, and RET also exhibited increased expression of these genes. We then searched for mutations and fusions in cancer driver genes in each sample and found that nine patients carried both mutations and fusions in cancer driver genes. Furthermore, we found a trend for mutual exclusivity between gene fusions and mutations in the same gene, with the exception of DMD, and we found that EGFR mutations are associated with the number of fusion genes. Finally, we identified kinase gene fusions, and potentially druggable fusions, which may play roles in lung cancer therapy. Conclusion: The clinical use of RNA-Seq for detecting driver fusion genes may play an important role in the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Point mutations of the K-ras gene located in codons 12 and 13 cause poor responses to the anti-epidermal growth factor receptor (anti-EGFR) therapy of colorectal cancer (CRC) patients. Besides, mutations of K-ras gene have also been proven to play an important role in human tumor progression. We established a simple and effective capillary electrophoresis (CE) method for simultaneous point mutation detection in codons 12 and 13 of K-ras gene. We combined one universal fluorescence-based nonhuman-sequence primer and two fragment-oriented primers in one tube, and performed this two-in-one polymerase chain reaction (PCR). PCR fragments included wild type and seven point mutations at codons 12 and 13 of K-ras gene. The amplicons were analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE analysis was performed by using a 1× Tris–borate–EDTA (TBE) buffer containing 1.5% (w/v) hydroxyethylcellulose (HEC) (MW 250 000) under reverse polarity with 15°C and 30°C. Ninety colorectal cancer patients were blindly genotyped using this developed method. The results showed good agreement with those of DNA sequencing method. The SSCP-CE was feasible for mutation screening of K-ras gene in populations. [Copyright &y& Elsevier]