Unveiling the Impact of the Genomic Architecture on the Evolution of Vertebrate microRNAs.

Eukaryotic genomes frequently exhibit interdependency between transcriptional units, as evidenced by regions of high gene density. It is well recognized that vertebrate microRNAs (miRNAs) are usually embedded in those regions. Recent work has shown that the genomic context is of utmost importance to determine miRNA expression in time and space, thus affecting their evolutionary fates over long and short terms.

Intratumoral Genetic Heterogeneity in Rectal Cancer: Are Single Biopsies representative of the entirety of the tumor?

Objective: Demonstrate intratumoral genetic heterogeneity in rectal cancer.

Background: Several clinical management decisions in rectal cancer may be influenced by pretreatment biopsy information. However, in the setting of significant intratumoral heterogeneity, biopsies may not be representative of the entirety of the tumor and limit the reliability of the information provided from them for clinical decision management.

Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma.

Background: Glioblastoma (GBM) is the most common and aggressive type of brain tumor. Currently, GBM has an extremely poor outcome and there is no effective treatment. In this context, genomic and transcriptomic analyses have become important tools to identify new avenues for therapies.

Host gene constraints and genomic context impact the expression and evolution of human microRNAs.

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes. Here we conjecture that human miRNA evolution is tightly influenced by the genomic context, especially by host genes. Our findings show a preferential emergence of intragenic miRNAs within old genes.

MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature.

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response.

Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice.

Cancer gene panels (CGPs) are already used in clinical practice to match tumor's genetic profile with available targeted therapies. We aimed to determine if CGPs could also be applied to estimate tumor mutational load and predict clinical benefit to PD-1 and CTLA-4 checkpoint blockade therapy. Whole-exome sequencing (WES) mutation data obtained from melanoma and non-small cell lung cancer (NSCLC) patients published by Snyder et al.

A Genome-Wide Landscape of Retrocopies in Primate Genomes.

Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates.

Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) may lead to complete tumor regression in rectal cancer patients. Prediction of complete response to nCRT may allow a personalized management of rectal cancer and spare patients from unnecessary radical total mesorectal excision with or without sphincter preservation. To identify a gene expression signature capable of predicting complete pathological response (pCR) to nCRT, we performed a gene expression analysis in 25 pretreatment biopsies from patients who underwent 5FU-based nCRT using RNA-Seq.

Alternative polyadenylation allows differential negative feedback of human miRNA miR-579 on its host gene ZFR.

About half of the known miRNA genes are located within protein-coding host genes, and are thus subject to co-transcription. Accumulating data indicate that this coupling may be an intrinsic mechanism to directly regulate the host gene's expression, constituting a negative feedback loop. Inevitably, the cell requires a yet largely unknown repertoire of methods to regulate this control mechanism.

Identification of agonists for a group of human odorant receptors.

Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs) which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose.

ICRmax: an optimized approach to detect tumor-specific interchromosomal rearrangements for clinical application.

Somatically acquired chromosomal rearrangements occur at early stages during tumorigenesis and can be used to indirectly detect tumor cells, serving as highly sensitive and tumor-specific biomarkers. Advances in high-throughput sequencing have allowed the genome-wide identification of patient-specific chromosomal rearrangements to be used as personalized biomarkers to efficiently assess response to treatment, detect residual disease and monitor disease recurrence. However, sequencing and data processing costs still represent major obstacles for the widespread application of personalized biomarkers in oncology.

Overexpression of miR-21-5p as a predictive marker for complete tumor regression to neoadjuvant chemoradiotherapy in rectal cancer patients.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the preferred treatment strategy for locally advanced rectal cancer. However, complete tumor regression is observed in a significant proportion of patients after nCRT, making them ideal candidates for alternative treatment strategies to this considerably morbid procedure. Identification of such patients based on clinical findings (complete clinical response - cCR) is difficult mainly because it relies on subjective clinical and imaging studies.

miRIAD-integrating microRNA inter- and intragenic data.

MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum).

Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy.

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1).

Recurrent somatic mutation in DROSHA induces microRNA profile changes in Wilms tumour.

Wilms tumour (WT) is an embryonal kidney neoplasia for which very few driver genes have been identified. Here we identify DROSHA mutations in 12% of WT samples (26/222) using whole-exome sequencing and targeted sequencing of 10 microRNA (miRNA)-processing genes. A recurrent mutation (E1147K) affecting a metal-binding residue of the RNase IIIb domain is detected in 81% of the DROSHA-mutated tumours.

The human cell surfaceome of breast tumors.

Introduction: Cell surface proteins are ideal targets for cancer therapy and diagnosis. We have identified a set of more than 3700 genes that code for transmembrane proteins believed to be at human cell surface.

Methods: We used a high-throuput qPCR system for the analysis of 573 cell surface protein-coding genes in 12 primary breast tumors, 8 breast cell lines, and 21 normal human tissues including breast.

RCPedia: a database of retrocopied genes.

Motivation: Retrocopies are copies of mature RNAs that are usually devoid of regulatory sequences and introns. They have routinely been classified as processed pseudo-genes with little or no biological relevance. However, recent findings have revealed functional roles for retrocopies, as well as their high frequency in some organisms, such as primates.

SurfaceomeDB: a cancer-orientated database for genes encoding cell surface proteins.

Cell surface proteins (CSPs) are excellent targets for the development of diagnostic and therapeutic reagents, and it is estimated that 10-20% of all genes in the human genome encode CSPs. In an effort to integrate all data publicly available for genes encoding cell surface proteins, a database (SurfaceomeDB) was developed. SurfaceomeDB is a gene-centered portal containing different types of information, including annotation for gene expression, protein domains, somatic mutations in cancer, and protein-protein interactions for all human genes encoding CSPs.

Gene copy-number polymorphism caused by retrotransposition in humans.

The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance.

SPLOOCE: a new portal for the analysis of human splicing variants.

Understanding alternative splicing is crucial to elucidate the mechanisms behind several biological phenomena, including diseases. The huge amount of expressed sequences available nowadays represents an opportunity and a challenge to catalog and display alternative splicing events (ASEs). Although several groups have faced this challenge with relative success, we still lack a computational tool that uses a simple and straightforward method to retrieve, name and present ASEs.

Setting up an intronic miRNA database.

In the recent past, intragenic microRNAs (miRNAs) have gained significant attention. Due to the unique linkage to their host gene's transcription, these miRNAs offer more information than intergenic miRNAs as they associate with some of their hosts' properties. However, genome wide analysis of intronic miRNA data can be very challenging, especially if it relies on Web-based tools only.

Common promoter elements in odorant and vomeronasal receptor genes.

In mammals, odorants and pheromones are detected by hundreds of odorant receptors (ORs) and vomeronasal receptors (V1Rs and V2Rs) expressed by sensory neurons that are respectively located in the main olfactory epithelium and in the vomeronasal organ. Even though these two olfactory systems are functionally and anatomically separate, their sensory neurons show a common mechanism of receptor gene regulation: each neuron expresses a single receptor gene from a single allele. The mechanisms underlying OR and VR gene expression remain unclear.

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual.

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both.