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The initiation of prostate cancer has been long associated with DNA copy-number alter-ations, the loss of specific chromosomal regions and gene fusions, and driver mutations, especially those of the Androgen Receptor. Non-mutational events, particularly DNA and RNA epigenetic dysregulation, are emerging as key players in tumorigenesis. In this review we summarize the molecular changes linked to epigenetic and epitranscriptomic dysregulation in prostate cancer and the role that alterations to DNA and RNA modifications play in the initiation and progression of prostate cancer., This work was funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 grant PID2019-111692RB-I00. In addition, we acknowledge funding from The Scientific Foundation AECC (LABAE19040BLAN), the University of Salamanca and Fundación Memoria de Samuel Solorzano Barruso (FS/36-2020), and Consejería de Educación de la Junta de Castilla y León (CSI264P20) to S.B., A.M.A-G. was supported by USAL-Santander PhD fellowship. J.L. was supported by The Scientific Foundation AECC predoctoral fellowship (PRDSA19002LÓPE) and the Spanish Ministry of Universities predoctoral fellowship (FPU19/01190). The Instituto de Biología Molecular y Celular del Cancer is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia, co-financed by the Castilla–León autonomous government and the European Regional Development Fund (CLC–2017–01).

On behalf of the PETHEMA Group, Spanish Society of Hematology., [Background]: Pediatric‐based or ‐inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome‐negative (Ph‐neg) acute lymphoblastic leukemia (ALL)., [Methods]: This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15‐30 years with standard‐risk (SR) ALL., [Results]: From 2008 to 2018, 89 patients (38 adolescents [15‐18 years] and 51 young adults [YA, 19‐30 years], median age: 20 [15‐29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty‐two patients were transferred to a high‐risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high‐level of end‐induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%‐47%), with significant differences between adolescents and YA: 13% (4%‐28%) vs 52% (34%‐67%), P = .012. No treatment‐related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5‐year overall survival (OS) was 74% (95%CI: 63%‐85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%‐100%) vs 63% (46%‐80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%‐47%] vs 37% [14%‐61%]; OS: 78% [66%‐90%] vs 61% [31%;91%])., [Conclusion]: A full pediatric trial is feasible and effective for AYA with Ph‐neg, SR‐ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior., We thanks to the following institutions from Spain their support for this paper: ICO‐Hospital Germans Trias i Pujol. Josep Carreras Research Institute. Universitat Autònoma de Barcelona. Hospital Universitari i Politècnic La Fe, Valencia. Hospital Clínico Valencia. Hospital Central de Asturias, Oviedo. Hospital Universitario Virgen del Rocío, Sevilla. Hospital General Universitario de Alicante. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona. Hospital General Universitario de Castellón. ICO‐Hospital Josep Trueta, Girona. Hospital Dr Peset, Valencia. ICO‐Hospital Duran i Reynals, L'Hospitalet de Llobregat. Hospital Son Espases, Palma de Mallorca. Hospital Clínico Universitario, Cancer Research Center (IBMCC‐CSIC/USAL), Cytometry Service, Salamanca. Hospital San Pedro de Alcántara, Cáceres. Hospital Morales Meseguer, Murcia. Hospital Mútua de Terrassa, Terrassa. Hospital Doce de Octubre, Madrid. Hospital Ramón y Cajal, Madrid. Hospital de Sant Pau, Barcelona. Hospital Arnau de Vilanova, Lleida. Hospital Lucus Augusti, Lugo. ICO‐Hospital Joan XXIII, Tarragona.

Summary Mammalian gametogenesis involves dramatic and tightly regulated chromatin remodeling, whose regulatory pathways remain largely unexplored. Here, we generate a comprehensive high-resolution structural and functional atlas of mouse spermatogenesis by combining in situ chromosome conformation capture sequencing (Hi-C), RNA sequencing (RNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) of CCCTC-binding factor (CTCF) and meiotic cohesins, coupled with confocal and super-resolution microscopy. Spermatogonia presents well-defined compartment patterns and topological domains. However, chromosome occupancy and compartmentalization are highly re-arranged during prophase I, with cohesins bound to active promoters in DNA loops out of the chromosomal axes. Compartment patterns re-emerge in round spermatids, where cohesin occupancy correlates with transcriptional activity of key developmental genes. The compact sperm genome contains compartments with actively transcribed genes but no fine-scale topological domains, concomitant with the presence of protamines. Overall, we demonstrate how genome-wide cohesin occupancy and transcriptional activity is associated with three-dimensional (3D) remodeling during spermatogenesis, ultimately reprogramming the genome for the next generation., Graphical Abstract, Highlights • Meiotic and post-meiotic cells differ in their hierarchal genome organization • Meiotic cohesin loading correlates with gene expression and local insulation • Sperm cells contain compartments with active transcription but no clear TADs • Genes that escape X chromosome silencing associate with promoter cohesin occupancy, The formation of mammalian germ cells involves dramatic chromosomal movements and chromatin remodeling, whose regulatory pathways are far from understood. Vara et al. show how the dynamics of insulator proteins’ occupancy and transcriptional activity are coupled during the 3D genome re-organization that takes place during mouse spermatogenesis.

© The Author(s)., [Background]: Ring chromosome 15 has been associated in previous studies with different clinical characteristic such as cardiac problems, digit and musculoskeletal abnormalities, and mental and motor problems among others. Only 97 clinical cases of ring chromosome 15 syndrome have been reported since 1966 and a common phenotype for these patients has not been established., [Case presentation]: The present case report describes a 15-month-old girl from the Amazon region of Ecuador, of Mestizo ancestry, who after cytogenetic tests showed a 46,XX,r(15) karyotype in more than 70% of metaphases observed. Her parents were healthy and non-related. The pregnancy was complicated and was positive for intrauterine growth retardation. Her birth weight was 1950 g, her length was 43.5 cm, and she had a head circumference of 29.3. In addition to postnatal growth delay, she had scant frontal hair, small eyes, hypertelorism, low-set of ears, flattened nasal bridge, anteverted nostrils, down-turned mouth, three café au lait spots, and delayed dentition., [Conclusions]: Despite the frequency of some phenotypes expressed in the different clinical cases reviewed and the present case, a common phenotype for patients with ring 15 could not be determined and it is restricted to the region of the chromosome lost during the ring formation., Funding for this research was completely managed by the institutions affiliated. Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador. Facultad de Ciencias de la Salud, Universidad San Francisco de Quito, Quito, Ecuador. Unidad de Investigación en Biomedicina, Zurita & Zurita Laboratorios, Quito, Ecuador. Servicio de Hematología, Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain. Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain. Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-SACYL-CSIC, Salamanca, Spain.

Memoria presentada por Iria Barcia Sanjurjo, graduada en Ciencia y Tecnología de los Alimentos para optar al grado de Doctor en Bioquímica y Biología Molecular por la Universidad de Santiago de Compostela (Departamento de Bioquímica y Biología Molecular) y realizada en el Instituto de Biología Molecular y Celular del Cancer de Salamanca., Esta Tesis Doctoral ha sido realizada dentro del Proyecto de Investigación Zimofeed: 08MMA003CT financiado por la Secretaria Xeral de Investigación e Desenvolvemento da Xunta de Galicia. Doña Iria Barcia Sanjurjo ha disfrutado de un contrato predoctoral financiado por la Vicerrectoría de Investigación e Innovación junto con el Departamento de Bioquímica y Biología Molecular de la Universidad de Santiago de Compostela. La investigación en el laboratorio del Centro de Investigación del Cancer (CIC-C.S.I.C) ha sido financiada por los siguientes proyectos: Ministerio de Educación y Ciencia (SAF2004-02900; SAF2007-60242; CDS-2007-0017 y SAF2010-14935). Junta de Castilla y León, Consejería de Sanidad (SAN/673/SA05/08; BOCyL Nº 170). Junta de Castilla y León, Consejería de Educación (CSI14A08; CSI006A11-2 y grupo de excelencia GR-15). Kutxa-Fundación INBIOMED.

Several studies have evaluated the prognostic value of the individual expression of certain genes in patients with myelodysplastic syndromes (MDS). However, none of them includes their simultaneous analysis by quantitative polymerase chain reaction (PCR). We evaluated relative expression levels of 14 molecular markers in 193 peripheral blood samples from untreated MDS patients using real-time PCR. Detectable WT1 expression levels, low TET2, and low IER3 gene expression were the only markers showing in univariate analysis a poor prognostic value for all treatment-free (TFS), progression-free (PFS), and overall survival (OS). In multivariate analysis, molecular parameters associated with a shorter TFS were: WT1 detection (p=0.014), low TET2 (p=0.002), and low IER3 expression (p=0.025). WT1 detection (p=0.006) and low TET2 (p=0.006) expression were associated with a shorter PFS when multivariate analysis was carried out by including only molecular markers. Molecular values with an independent value in OS were: WT1 detection (p=0.003), high EVI1 expression (p=0.001), and undetectatable p15-CDKN2B (p=0.037). WT1 expressers were associated with adverse clinical-biological features, high IPSS and WPSS scoring, and unfavorable molecular expression profile. In summary, detectable WT1 expression levels, and low TET2 and low IER3 expression in peripheral blood showed a strong association with adverse prognosis in MDS patients at diagnosis. However, WT1 was the only molecular marker displaying an independent prognostic value in both OS and TFS., This work has been partially supported by the grants PI061351 and 00/0023-00 from the Spanish “Fondo de Investigaciones Sanitarias de la Seguridad Social”, 89/A/06 from the “Gerencia Regional de Salud, Junta Castilla y León”, and CIC, IBMCC (USAL-CSIC), Spain. The Spanish MDS Group (GESMD), provided samples and clinical information from patients participating in the INBIOMED HEMA-001/2006 project (sponsored by Celgene S.L., Madrid).

This is an open access article under the CC BY-NC-ND license., Plasmodium vivax is the second most prevalent parasite species causing malaria in humans living in tropical and subtropical areas throughout the world. There have been few P. vivax proteomic studies to date and they have focused on using clinical isolates, given the technical difficulties concerning how to maintain an in vitro culture of this species. This study was thus focused on identifying the P. vivax VCG-1 strain proteome during its blood lifecycle through LC-MS/MS; this led to identifying 734 proteins, thus increasing the overall number reported for P. vivax to date. Some of them have previously been related to reticulocyte invasion, parasite virulence and growth and others are new molecules possibly playing a functional role during metabolic processes, as predicted by Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis. This is the first large-scale proteomic analysis of a P. vivax strain adapted to a non-human primate model showing the parasite protein repertoire during the blood lifecycle. Database searches facilitated the in silico prediction of proteins proposed for evaluation in further experimental assays regarding their potential as pharmacologic targets or as component of a totally efficient vaccine against malaria caused by P. vivax. Biological significance: P. vivax malaria continues being a public health problem around world. Although considerable progress has been made in understanding genome- and transcriptome-related P. vivax biology, there are few proteome studies, currently representing only 8.5% of the predicted in silico proteome reported in public databases. A high-throughput proteomic assay was used for discovering new P. vivax intra-reticulocyte asexual stage molecules taken from parasites maintained in vivo in a primate model. The methodology avoided the main problem related to standardising an in vitro culture system to obtain enough samples for protein identification and annotation. This study provides a source of potential information contributing towards a basic understanding of P. vivax biology related to parasite proteins which are of significant importance for the malaria research community., We would also like to thank the ProteoRed, PRB2-ISCIII proteomics facility at the Instituto de Biología Molecular y Celular del Cáncer USAL-CSIC, financed by grant PT13/0001. This research was supported by the “Instituto Colombiano para el Desarrollo de la Ciencia ‘Francisco José de Caldas’” (COLCIENCIAS) through contracts RC#309-2013 and 709-2013.