Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7.

Background & Aims: The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC.

TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk.

Background And Aims: Major genomic drivers of hepatocellular carcinoma (HCC) are nowadays well recognized, although models to establish their roles in human HCC initiation remain scarce. Here, we used human liver organoids in experimental systems to mimic the early stages of human liver carcinogenesis from the genetic lesions of TP53 loss and L3 loop R249S mutation. In addition, chromatin immunoprecipitation sequencing (ChIP-seq) of HCC cell lines shed important functional insights into the initiation of HCC consequential to the loss of tumor-suppressive function from TP53 deficiency and gain-of-function activities from mutant p53.

Overexpression of nucleotide metabolic enzyme DUT in hepatocellular carcinoma potentiates a therapeutic opportunity through targeting its dUTPase activity.

Uracil misincorporation during DNA replication is a major cell toxic event, of which cancer cells overcome by activating the dUTPase enzyme. The DUT gene is the only known dUTPase in human. Despite reports on common upregulations in cancers, the role of DUT in human hepatocellular carcinoma (HCC) remains largely undetermined.

Unique molecular characteristics of NAFLD-associated liver cancer accentuate β-catenin/TNFRSF19-mediated immune evasion.

Background & Aims: The hepatic manifestation of the metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), can lead to the development of hepatocellular carcinoma (HCC). Despite a strong causative link, NAFLD-HCC is often underrepresented in systematic genome explorations.

Methods: Herein, tumor-normal pairs from 100 patients diagnosed with NAFLD-HCC were subject to next-generation sequencing.

Organoids in Lung Cancer Management.

Lung cancer is a complex milieu of genomically altered cancer cells, a diverse collection of differentiated cells and nonneoplastic stroma. Lung cancer organoids is a three-dimensional structure grown from patient cancer tissue that could mimic complex behavior and cellular architecture of the cancer. Furthermore, the genomic alterations of the primary lung tumor is captured .

Patient-derived tumor organoid predicts drugs response in glioblastoma: A step forward in personalized cancer therapy?

Despite significant medical advances, glioblastoma multiforme (GBM) remains a formidable therapeutic challenge. Advent of targeted capture sequencing and patients-derived organoid cultures may hold the key to scientifically sound individualized treatment approaches. We report on our initial experience of using the combination of these two technologies to create a tailored approach of systemic therapies for a patient with GBM, which challenges the conventional treatment paradigm, as well as specifically highlighting the complexities of such an approach and the potential for a more favorable treatment outcome.

Personalized therapy for hepatocellular carcinoma: Where are we now?

Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug.

Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma.

Apart from β-catenin accumulation, loss of 3p21 is one of the most frequent genetic alterations in numerous malignancies including nasopharyngeal carcinoma (NPC). Herein, we characterized a novel candidate tumor suppressor gene (TSG) CACNA2D3, a voltage-dependent subunit alpha 2 delta 3 of a calcium channel complex. Downregulation of CACNA2D3 was frequently detected in primary NPCs and NPC cell lines compared with their nontumorigenic counterparts.

MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN.

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with significantly high prevalence in Southern China. Unlike other head and neck cancers, mutations or deletions of tumor suppressor genes in NPC are not common. Recently, downregulation of tumor suppressor genes expression by microRNA (miRNA) is increasingly recognized as an important mechanism of nasopharyngeal tumorigenesis.

RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis.

Deletion of the short arm of chromosome 3 is one of the most frequent genetic alterations in many solid tumors including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3 (RNA binding motif, single stranded interacting protein 3), located at 3p24-p23, has been identified in our previous study. Here, we reported that downregulation of RBMS3 was detected in 3/3 NPC cell lines and 13/15 (86.

Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs.

Background: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis.

Identification of genes with allelic imbalance on 6p associated with nasopharyngeal carcinoma in southern Chinese.

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC.