Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.

Urea as a key nitrogen source for the invasion of the southern coast of Portugal by the brown seaweed Rugulopteryx okamurae (Dyctiotales, Phaeophyceae).

The invasive seaweed Rugulopteryx okamurae, native to East Asia, is spreading rapidly along the western Mediterranean and southern Portugal, severely affecting coastal biodiversity, ecosystem structure, and economic sectors such as fisheries and tourism. This study examined the nutrient uptake kinetics of R. okamurae, including ammonium, nitrate, urea, amino acids, and phosphate, and their role in nitrogen and phosphorus budgets based on laboratory growth rates.

Noncoding mutations drive persistence of a founder preleukemic clone which initiates late relapse in T-ALL.

T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.

Diurnal source apportionment of organic and inorganic atmospheric particulate matter at a high-altitude mountain site under summer conditions (Sierra Nevada; Spain).

High-altitude mountain areas are sentinel ecosystems for global environmental changes such as anthropogenic pollution. In this study, we report a source apportionment of particulate material with an aerodynamic diameter smaller than 10 μm (PM) in a high-altitude site in southern Europe (Sierra Nevada Station; SNS (2500 m a.s.

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression.

Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Transcriptional silencing via TRIM28 maps to a 190 bp sequence encoding the intracisternal A-type particle (IAP) signal peptide, which confers retrotransposition activity.

The Clinicogenomic Landscape of Induction Failure in Childhood and Young Adult T-Cell Acute Lymphoblastic Leukemia.

Purpose: Failure to respond to induction chemotherapy portends a poor outcome in childhood acute lymphoblastic leukemia (ALL) and is more frequent in T-cell ALL (T-ALL) than B-cell ALL. We aimed to address the limited understanding of clinical and genetic factors that influence outcome in a cohort of patients with T-ALL induction failure (IF).

Methods: We studied all cases of T-ALL IF on two consecutive multinational randomized trials, UKALL2003 and UKALL2011, to define risk factors, treatment, and outcomes.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome.

A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.

Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency.

Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone.

Oncohistones represent compelling evidence for a causative role of epigenetic perturbations in cancer. Giant cell tumours of bone (GCTs) are characterised by a mutated histone H3.3 as the sole genetic driver present in bone-forming osteoprogenitor cells but absent from abnormally large bone-resorbing osteoclasts which represent the hallmark of these neoplasms.

Adaptation of the Multidimensional Body Self Relations Questionnaire for Young People Between 9 and 16 Years old.

Background: Young adolescents and pre-adolescents are the population most vulnerable to disorders derived from a distorted Body Image (BI). In this study, the Multidimensional Body Self Relations Questionnaire, MBSR®, was adapted and validated for young Spanish people between 9 and 16 years old.

Method: 719 young people of both sexes participated.

Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors.

Purpose: The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined.

Experimental Design: Herein, we studied 40 patients with primary and synchronous metastatic siNETs, and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry.

The Th1 cell regulatory circuitry is largely conserved between human and mouse.

Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases.

Analysis of genetic diversity and discrimination of Oil Palm DxP populations based on the origins of pisifera elite parents.

A total of 251 Dura cross Pisifera (DxP) hybrid palms from six populations descending from six parental African Pisifera origins and involving 12 progenies were analyzed with 19 selected Simple Sequence Repeats (SSR) markers. A total of 110 alleles were produced, ranging from three to eight per SSR, with a mean of 5.8 alleles per SSR locus.

Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms.

Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients with neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffin-embedded (FFPE), and fresh frozen (FF) samples.

Nascent RNA antagonizes the interaction of a set of regulatory proteins with chromatin.

A number of regulatory factors are recruited to chromatin by specialized RNAs. Whether RNA has a more general role in regulating the interaction of proteins with chromatin has not been determined. We used proteomics methods to measure the global impact of nascent RNA on chromatin in embryonic stem cells.

Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion.

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment.

Increased Immune-Regulatory Receptor Expression on Effector T Cells as Early Indicators of Relapse Following Autologous Stem Cell Transplantation for Multiple Myeloma.

The benefit of autologous stem cell transplantation (ASCT) in newly diagnosed myeloma patients, apart from supporting high dose chemotherapy, may include effects on T cell function in the bone marrow (BM). We report our exploratory findings on marrow infiltrating T cells early post-ASCT (day+100), examining phenotype and T cell receptor (TCR) repertoire, seeking correlations with timing of relapse. Compared to healthy donors (HD), we observed an increase in regulatory T cells (CD4+FoxP3+, Tregs) with reduction in CD4 T cells, leading to lower CD4:8 ratios.

Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.

Frameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels are degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysis, expressed fs-indels are enriched in genomic positions predicted to escape NMD, and associated with higher protein expression, consistent with degradation escape (NMD-escape).

Construction of a high density linkage map in Oil Palm using SPET markers.

A high-density genetic linkage map from a controlled cross of two oil palm (Elaeis guineensis) genotypes was constructed based on Single Primer Enrichment Technology (SPET) markers. A 5K panel of hybridization probes were used for this purpose which was derived from previously developed SNP primers in oil palm. Initially, 13,384 SNPs were detected which were reduced to 13,073 SNPs after filtering for only bi-allelic SNP.