Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer.

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes.

MIXnorm: normalizing RNA-seq data from formalin-fixed paraffin-embedded samples.

Motivation: Recent studies have shown that RNA-sequencing (RNA-seq) can be used to measure mRNA of sufficient quality extracted from formalin-fixed paraffin-embedded (FFPE) tissues to provide whole-genome transcriptome analysis. However, little attention has been given to the normalization of FFPE RNA-seq data, a key step that adjusts for unwanted biological and technical effects that can bias the signal of interest. Existing methods, developed based on fresh-frozen or similar-type samples, may cause suboptimal performance.

RCRnorm: An integrated system of random-coefficient hierarchical regression models for normalizing NanoString nCounter data.

Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies, and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity, which may greatly facilitate realization of scientific and clinical values of FFPE samples.

Genetic and Epigenetic Features of Rapidly Progressing IDH-Mutant Astrocytomas.

IDH-mutant astrocytomas are significantly less aggressive than their IDH-wildtype counterparts. We analyzed The Cancer Genome Atlas dataset (TCGA) and identified a small group of IDH-mutant, WHO grade II-III astrocytomas (n = 14) with an unexpectedly poor prognosis characterized by a rapid progression to glioblastoma and death within 3 years of the initial diagnosis. Compared with IDH-mutant tumors with the typical, extended progression-free survival in a control group of age-similar patients, the tumors in the rapidly progressing group were characterized by a markedly increased level of overall copy number alterations ([CNA]; p = 0.

Probability of phenotypically detectable protein damage by ENU-induced mutations in the Mutagenetix database.

Computational inference of mutation effects is necessary for genetic studies in which many mutations must be considered as etiologic candidates. Programs such as PolyPhen-2 predict the relative severity of damage caused by missense mutations, but not the actual probability that a mutation will reduce/eliminate protein function. Based on genotype and phenotype data for 116,330 ENU-induced mutations in the Mutagenetix database, we calculate that putative null mutations, and PolyPhen-2-classified "probably damaging", "possibly damaging", or "probably benign" mutations have, respectively, 61%, 17%, 9.

A permutation-based non-parametric analysis of CRISPR screen data.

Background: Clustered regularly-interspaced short palindromic repeats (CRISPR) screens are usually implemented in cultured cells to identify genes with critical functions. Although several methods have been developed or adapted to analyze CRISPR screening data, no single specific algorithm has gained popularity. Thus, rigorous procedures are needed to overcome the shortcomings of existing algorithms.

Exome Sequencing of Normal and Isogenic Transformed Human Colonic Epithelial Cells (HCECs) Reveals Novel Genes Potentially Involved in the Early Stages of Colorectal Tumorigenesis.

Background: We have generated a series of isogenically derived immortalized human colonic epithelial cell (HCEC 1CT and HCEC 2CT) lines, including parental un-immortalized normal cell strains. The CDK4 and hTERT immortalized colonic epithelial cell line (HCEC 1CT) is initially karyotypically normal diploid and expresses a series of epithelial cell markers including stem cell markers. Under stressful tissue culture conditions, a spontaneous aneuploidy event occurred in the HCEC 1CT line, resulting in a single chromosomal change leading to a stable trisomy 7 cell line (1CT7).

Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways.

Introduction: Metastasis is the main cause of breast cancer morbidity and mortality. Processes that allow for tumor cell migration and invasion are important therapeutic targets. Here we demonstrate that receptor-interacting protein kinase 2 (RIP2), a kinase known to be involved in inflammatory processes, also has novel roles in cancer cell migration and invasion.

Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging.

With the characterization of Sir2 gene in yeast aging, its mammalian homologs Sirtuins 1–7 have been attracting attention from scientists with various research backgrounds. Among Sirtuins, SIRT1 is the most extensively studied. Recent progress on mammalian Sirtuins has shown that SIRT6 as a histone deacetylase may also play a critical role in regulating mammalian aging.