Somatic Mutaome Profile in Human Cancer Tissues

Somatic mutation is a major cause of cancer progression and varied responses of tumors against anticancer agents. Thus, we must obtain and characterize genome-wide mutational profiles in individual cancer subtypes. The Cancer Genome Atlas database includes large amounts of sequencing and omics data generated from diverse human cancer tissues. In the present study, we integrated and analyzed the exome sequencing data from ~3,000 tissue samples and summarized the major mutant genes in each of the diverse cancer subtypes and stages. Mutations were observed in most human genes (~23,000 genes) with low frequency from an analysis of 11 major cancer subtypes. The majority of tissue samples harbored 20-80 different mutant genes, on average. Lung cancer samples showed a greater number of mutations in diverse genes than other cancer subtypes. Only a few genes were mutated with over 5% frequency in tissue samples. Interestingly, mutation frequency was generally similar between non-metastatic and metastastic samples in most cancer subtypes. Among the 12 major mutations, the TP53, USH2A, TTN, and MUC16 genes were found to be frequent in most cancer types, while BRAF, FRG1B, PBRM1, and VHL showed lineage-specific mutation patterns. The present study provides a useful resource to understand the broad spectrum of mutation frequencies in various cancer types

Additional file 1: of QSurface: fast identification of surface expression markers in cancers

Table S1. Data description of TCGA RNA sequencing data. Table S2. List of antibody-drug conjugates. Figure S1. Distribution of tumor sample-specific gene expression in 14 cancer types. Totally 20,531 genes, 519 cell surface marker, and significant cell surface hits (log2Delta > 1 and p-value < 0.01) are illustrated in grey, yellow, and red, respectively. Figure S2. Western blot analysis of the MUC 4, MSLN and SLC7A11 expression on STK11 mutant, restored and wild type cell lines. (A) gene expression on STK11 mutant, restored and wild-type cell lines on 2D culture status and (B) on 3D culture status. (DOCX 1902 kb

Cancer cells undergoing epigenetic transition show short-term resistance and are transformed into cells with medium-term resistance by drug treatment

Cancer chemotherapy: treatment prolongs resistance caused by DNA modification Cancer cells that are transiently resistant to drug therapies owing to changes in their gene expression patterns can become resistant for longer durations if exposed to the drug treatments. A team led by Kyeong-Man Hong and Hyonchol Jang from the National Cancer Center in Goyang, South Korea, used cellular reprogramming technologies to induce changes in the DNA markers that regulate gene expression. Working with lung and gastric cancer cell lines, the researchers found that such epigenetic alterations caused many cells to become resistant to the chemotherapy drugs cisplatin and paclitaxel. In the absence of treatment, the cells soon lost their drug resistance. In the presence of the chemotherapeutics, however, the resistance trait lasted longer, a finding that could inform best practice for how to administer cancer-fighting agents in the face of epigenetic-driven drug resistance

Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer

Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.status: publishe