The high degree of heterogeneity observed in breast cancers makes it very difficult to classify the cancer patients into distinct clinical subgroups and consequently limits ability devise effective therapeutic strategies. Several classification strategies based on ER/PR/HER2 expression or profiles a panel genes have helped, but such methods often produce misleading results due their dynamic nature. In contrast, somatic DNA mutations are relatively stable lead initiation progression many...

Abstract Background Small cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. SCLC progression and treatment resistance involve epigenetic processes. However, links between DNA methylation drug response remain unclear. We performed epigenome-wide study of 66 human lines using the Illumina Infinium MethylationEPIC BeadChip array. Correlations gene expression with in vitro to 526 antitumor agents were examined. Results found multiple significant correlations chemosensitivity. A...

Abstract Large cell (LCNEC), prostate (NEPC) and small lung (SCLC) neuroendocrine carcinomas are highly aggressive malignancies with few therapeutic options. Lurbinectedin, is an FDA-approved DNA-damaging agent used for the treatment of SCLC, although its efficacy remains limited. Our group has found that (NE) tumors have higher levels DNA damage repair (DDR) proteins than non-NE tumors, which may contribute to their reduced response agents. Exportin 1 (XPO-1), export receptor regulates DDR...

Abstract Background Understanding protein subcellular localization is a necessary component toward understanding the overall function of protein. Numerous computational methods have been published over past decade, with varying degrees success. Despite large number in this area, only small fraction them are available for researchers to use their own studies. Of those that available, many limited by predicting organelles cell. Additionally, majority predict single location sequence, even...

Breast cancers exhibit highly heterogeneous molecular profiles. Although gene expression profiles have been used to predict the risks and prognostic outcomes of breast cancers, high variability limits its clinical application. In contrast, genetic mutation would be more advantageous than because mutations can stably detected mutational heterogeneity widely exists in cancer genomes. We analyzed 98 whole exome samples that were sorted into three subtypes, two grades stages. The sum deleterious...

Abstract Background In protein sequence classification, identification of the motifs or n -grams that can precisely discriminate between classes is a more interesting scientific question than classification itself. A number methods aim at accurate but fail to explain which features indeed contribute accuracy. We hypothesize sequences in lower denominations ( -grams) be used explore landscape and identify class-specific during classification. Discriminative are short peptide highly frequent...

Abstract Background Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved demethylation may be associated with response cell lines to chemotherapy treatment a variety antitumor agents. Results analyzed 72 encoding epigenetic factors processes. association their pretreatment beta-values individual probes, averaged within gene regions, average epigenome-wide levels. data from...

Splice site variants may lead to transcript alterations, causing exons inclusion, exclusion, truncation, or intron retention. Interpreting the consequences of a specific splice variant is not straightforward, especially if located outside canonical sites. We developed MutSpliceDB: https://brb.nci.nih.gov/splicing, public resource facilitate interpretation sites effects on splicing based manually reviewed RNA-seq BAM files from samples with variants.

The APOBEC gene family of cytidine deaminases plays important roles in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation load, generating clusters closely spaced, single-strand-specific substitutions with a characteristic hypermutation signature. Some studies also suggested possible involvement APOBEC3A, REV1, UNG, FHIT molecular processes affecting mutagenesis. It is to understand how mutagenic linked activity these genes may affect sensitivity cancer cells...

Abstract Small cell lung cancer (SCLC) is an aggressive form of with limited therapeutic options, a very high mortality rate and characterized, in most cases, by neuroendocrine features. A small but important subset SCLC has intact RB1. However, other characteristics this are not well-defined. To comprehensively assess the underlying genomics lines functional RB1, we examined 48 from Cancer Cell Line Encyclopedia (CCLE) collection. Out these lines, 8 were found to be RB1 WT. We that WT...

Tumor-suppressor genes can be inactivated by several mechanisms and, in a majority of cases, both alleles need to affected. One the inactivation is due deletions ranging from dozen hundreds nucleotides; such are often missed variant callers. HomDelDetect method detect homozygous cancer models, as cell lines and potentially patient tumor-derived xenografts. This applied partial exome, whole-exome sequencing, whole-genome RNA-seq data. We our across panel CCLE observed good concordance with...

Abstract Background Parent of origin-specific allelic expression imprinted genes is epigenetically controlled. In cancer, undergo both genomic and epigenomic alterations, including frequent copy number changes. We investigated whether loss or gain in cancer cell lines associated with response to chemotherapy treatment. Results analyzed 198 human protein-coding noncoding RNA using data from tumor the Cancer Cell Line Encyclopedia Genomics Drug Sensitivity datasets. examined 35 different...

Abstract The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) gene family of cytidine deaminases includes evolutionarily conserved genes that play important roles in DNA repair and editing. Activity at least two members, APOBEC3A APOBEC3B, can lead to kataegis, a mutagenic process cancer cells generates clusters closely spaced, single strand specific C->T substitutions. mutagenesis has characteristic signature, most commonly represented by the...

In this article, we introduce a hierarchical clustering and Gaussian mixture model with expectation-maximization (EM) algorithm for detecting copy number variants (CNVs) using whole exome sequencing (WES) data. The R shiny package 'HCMMCNVs' is also developed processing user-provided bam files, running CNVs detection conducting visualization. Through applying our approach to 325 cancer cell lines in 22 tumor types from Cancer Cell Line Encyclopedia (CCLE), show that competitive other...

Abstract TP53 is one of the most frequently altered genes in cancer; it can be inactivated by a number different mechanisms. NM_000546.6 (ENST00000269305.9) far predominant isoform, however few other alternative isoforms have been described to expressed at much lower levels. To better understand patterns expression cancer and normal samples we performed exon-exon junction reads based analysis using RNA-seq data from The Cancer Genome Atlas (TCGA), Cell Line Encyclopedia (CCLE),...

Abstract We used gene expression information and mutational signature analysis of cell lines from a diverse range cancerous tissues to examine the activity two members APOBEC family cytidine deaminases, APOBEC3A APOBEC3B, three additional genes. APOBEC3B is known increase mutation load in many cancers, generating kataegis clusters closely spaced, single strand-specific DNA substitutions with characteristic hypermutation signature. Some studies also suggested that APOBEC3A, REV1, UNG, FHIT...

Folate-mediated one-carbon metabolism (OCM) is essential for growth and survival of cancer cells. It affects biosynthesis nucleotides amino acids, regulation redox status, methylation nucleic acids proteins, genome maintenance. We investigated whether the response cells to antitumor therapy treatment may be partially influenced by variation in expression genes. used publicly available gene data drug measures 251 agents 635 cell lines with matching information from Cancer Cell Line...

Abstract Splice site mutations are one of the well-known classes genetic alterations playing an important role in biology. cancer most frequently observed as inactivating tumor suppressor genes (for example, TP53 or RB1) and to a lesser degree activating oncogenes example MET). may lead mRNA transcripts, causing for exon(s) inclusion/exclusion or, intron retention. Interpreting consequences specific splice mutation is not straightforward, especially if located outside canonical sites....

DNA methylation has a powerful influence on cellular processes. It plays important roles in cancer initiation and progression. Cancer cells exhibit frequent epigenomic alterations that affect expression of genes involved apoptosis, cell proliferation, repair. We used information known methylating demethylating lines to analyze their association with levels individual probes median epigenome-wide levels. utilized RNA-seq gene measures Illumina Infinium HumanMethylation450 BeadChip data 645...

Abstract Small cell lung cancer (SCLC), an aggressive neuroendocrine type of cancer, rapidly acquires resistance to treatment. SCLC progression, lineage differentiation, and therapy have been suggested involve epigenetic processes. To date, links connecting DNA methylation patterns drug response the ways in which these are mediated by gene expression remain unclear. In order understand how may affect chemotherapy, we performed epigenome-wide association study 66 lines. We used Illumina...

Abstract DNA methylation has a powerful influence on cellular processes. It plays important roles in cancer initiation and progression. Cancer cells exhibit frequent epigenomic alterations that affect expression of genes involved apoptosis, cell proliferation, repair. We used information known methylating demethylating lines to analyze their association with levels individual probes median epigenome-wide levels. utilized RNA-seq gene measures Illumina Infinium HumanMethylation450 BeadChip...

Splice site mutations are one of the well-known classes genetic alterations playing an important role in biology. cancer most frequently observed as inactivating tumor suppressor genes (for example, TP53 or RB1) and to a lesser degree activating oncogenes example MET). may lead mRNA transcripts, causing for exon(s) inclusion/exclusion or, intron retention. Interpreting consequences specific splice mutation is not straightforward, especially if located outside canonical sites. Accurate...

Abstract Folate-mediated one-carbon metabolism (OCM) is essential for growth and survival of cancer cells. It affects biosynthesis nucleotides amino acids, regulation redox status, methylation nucleic acids proteins, genome maintenance. We investigated whether the response cells to antitumor therapy treatment may be partially influenced by variation in expression genes. used publicly available gene data drug measures 251 agents 635 cell lines with matching information from Cancer Cell Line...