Whole-Exome Sequencing Identifies Somatic Mutations Associated With Mortality in Metastatic Clear Cell Kidney Carcinoma

Clear cell renal cell carcinoma (ccRCC) is among the most aggressive histologic subtypes of kidney cancer, representing about 3% of all human cancers. Patients at stage IV have nearly 60% of mortality in 2–3 years after diagnosis. To date, most ccRCC studies have used DNA microarrays and targeted sequencing of a small set of well-established, commonly altered genes. An exception is the large multi-omics study of The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC), which identified new ccRCC genes based on whole exome-sequencing (WES) data, and molecular prognostic signatures based on transcriptomics, epigenetics and proteomics data. Applying WES to simultaneously interrogate virtually all exons in the human genome for somatic variation, here we analyzed the burden of coding somatic mutations in metastatic ccRCC primary tumors, and its association with patient mortality from cancer, in patients who received VEGF receptor-targeting drugs as the first-line therapy. To this end, we sequenced the exomes of ten tumor–normal pairs of ccRCC patient tissues from primary biopsies at>100× mean depth and called somatic coding variation. Mutation burden analysis prioritized 138 genes linked to patient mortality. A gene set enrichment analysis evidenced strong statistical support for the abundance of genes involved in the development of kidney cancer (p=2.31×10–9) and carcinoma (p=1.22×10–5), with 49 genes having direct links w...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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The objective of the present study was to investigate the mRNA levels of important miRNA machinery components, DICER1, DROSHA, DiGeroge syndrome critical region gene 8 (DGCR8), and Argonaute 2 (AGO2), and their correlations with clinicopathological characteristics of ccRCC using mRNA expression data from The Cancer Genome Atlas kidney clear cell carcinoma (TCGA KIRC) cohort and a Korean ccRCC cohort. mRNA levels of DICER1, DROSHA, and DGCR8 were significantly decreased in both cohorts. However, AGO2 was significantly downregulated only in the Korean ccRCC cohort. Additionally, positive correlations were observed between th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
This study identified 41  138 surgically treated RCC patients: Of these patients, 50.6% had right‐sided RCC, 59.5% were younger than 65 years of age, 63.8% were male, and 81.0% were Caucasian. The stage distribution was 67.0% (I), 9.5% (II), 17.1% (III), and 6.4% (IV). Patients with right‐sided RCC were more likely to have favorable clinicopathological features compared with patients with left‐sided RCC. In adjusted analyses, patients with right‐sided RCC showed significantly better CSS than those with left‐sided RCC within different subgroups including tumor size ≥10 cm (P = .004), age
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSION: It was the first report in the world of such a case. PMID: 31061254 [PubMed - as supplied by publisher]
Source: Journal of Nippon Medical School - Category: Universities & Medical Training Authors: Tags: J Nippon Med Sch Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Authors: Maleckaite R, Zalimas A, Bakavicius A, Jankevicius F, Jarmalaite S, Daniunaite K Abstract Metallothioneins are low‑weight cysteine‑rich proteins responsible for metal ion homeostasis in a cell and, thus, capable of regulating cell proliferation and differentiation. Deregulation of metallothionein genes has been reported in various human tumors. However, their role in renal cell carcinoma (RCC) has been poorly investigated. In the present study, we aimed to evaluate the importance of promoter DNA methylation of selected metallothionein genes for RCC. Based on the initial analysis of kidney renal clear c...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Abstract MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors. These synthetic compounds are tested in biochemical and cell proliferation assays, and six of them display potent i...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research
az-Piqueras Á, Salinas-Sánchez AS Abstract INTRODUCTION: Elevated mRNA expression of human telomerase reverse transcriptase (hTERT mRNA) is common in many types of tumors, participating in tumor growth and progression. Such expression has not been sufficiently examined in renal cancer. The goal of the present study was to quantify it and analyze its possible clinical value in the management of this pathology. PATIENTS AND METHODS: The study included 111 patients who underwent surgery for renal cell carcinoma (RCC) between 2015 and 2017. Tumor samples were taken from all patients and, in 94 of th...
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
Contributors : Yilong Zou ; Mudra Hegde ; John Doench ; Stuart L SchreiberSeries Type : OtherOrganism : Homo sapiensClear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCC tumors are distinguished by aberrant lipid and glycogen accumulation and are inherently refractory to a broad range of anti-cancer therapies. In the study associated with this dataset, we identified an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCC cells. However, the mediators of this sensitivity to ferroptosis are unknown. Here we...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research
Abstract The present case report describes a case of left renal clear cell carcinoma with brain, lung, para-aortic, and lymph node metastases (cT1bN1M1) in a 52-year-old Japanese male. The patient received sequential anticancer treatments with pazopanib, everolimus, and axitinib, but exhibited treatment-resistant tumor growth. Treatment with nivolumab resulted in a complete response in metastatic sites. However, the residual renal tumor, which was enhanced by contrast medium, required radical nephrectomy. Pathological analyses of the renal tumor revealed that it consisted of fibrotic and lymphocyte-infiltrated tis...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Mol Clin Oncol Source Type: research
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