Search results for "Asia"
showing 10 items of 2697 documents
A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
2019
No luminal; Subtipus intrínsec; Càncer de mama No luminal; Subtipo intrínseco; Cáncer de mama Non-luminal; Intrinsic subtype, Breast cancer Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estr…
Novel and known signals of selection for fat deposition in domestic sheep breeds from Africa and Eurasia
2018
International audience; Genomic regions subjected to selection frequently show signatures such as within-population reduced nucleotide diversity and outlier values of differentiation among differentially selected populations. In this study, we analyzed 50K SNP genotype data of 373 animals belonging to 23 sheep breeds of different geographic origins using the Rsb (extended haplotype homozygosity) and FST statistical approaches, to identify loci associated with the fat-tail phenotype. We also checked if these putative selection signatures overlapped with regions of high-homozygosity (ROH). The analyses identified novel signals and confirmed the presence of selection signature in genomic regio…
Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas.
2018
AbstractObjective The diagnosis of carcinoma in both the uterus and the ovary simultaneously is not uncommon and raises the question of synchronous primaries vs. metastatic disease. Targeted sequencing of sporadic synchronous endometrial and ovarian carcinomas has shown that such tumors are clonally related and thus represent metastatic disease from one site to the other. Our purpose was to investigate whether or not the same applies to Lynch syndrome (LS), in which synchronous cancers of the gynecological tract are twice as frequent as in sporadic cases, reflecting inherited defects in DNA mismatch repair (MMR). Methods MMR gene mutation carriers with endometrial or ovarian carcinoma or en…
Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma
2018
Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mu…
Differential staining of peripheral nuclear chromatin with Acridine orange implies an A-form epichromatin conformation of the DNA
2018
ABSTRACT The chromatin observed by conventional electron microscopy under the nuclear envelope constitutes a single layer of dense 30–35 nm granules, while ∼30 nm fibrils laterally attached to them, form large patches of lamin-associated domains (LADs). This particular surface “epichromatin” can be discerned by specific (H2A+H2B+DNA) conformational antibody at the inner nuclear envelope and around mitotic chromosomes. In order to differentiate the DNA conformation of the peripheral chromatin we applied an Acridine orange (AO) DNA structural test involving RNAse treatment and the addition of AO after acid pre-treatment. MCF-7 cells treated in this way revealed yellow/red patches of LADs atta…
SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective
2020
In less than five months, COVID-19 has spread from a small focus in Wuhan, China, to more than 5 million people in almost every country in the world, dominating the concern of most governments and public health systems. The social and political distresses caused by this epidemic will certainly impact our world for a long time to come. Here, we synthesize lessons from a range of scientific perspectives rooted in epidemiology, virology, genetics, ecology and evolutionary biology so as to provide perspective on how this pandemic started, how it is developing, and how best we can stop it.
ATR expands embryonic stem cell fate potential in response to replication stress
2020
Fondazione Italiana per la Ricerca sul Cancro FIRC 18112 Sina Atashpaz.Fondazione Umberto Veronesi Sina Atashpaz Associazione Italiana per la Ricerca sul Cancro AIRC 5xmille METAMECH program Vincenzo Costanzo Giovanni Armenise-Harvard Foundation Vincenzo Costanzo European Research Council Consolidator grant 614541 Vincenzo Costanzo Associazione Italiana per la Ricerca sul Cancro Fellowship 23961 Negar ArghavanifarDanish Cancer Society KBVU-2014 Andres Joaquin Lopez-Contreras Danish Council for Independent Research Sapere Aude, DFF Starting Grant 2014 Andres Joaquin Lopez-Contreras European Research Council ERC-2015-STG-679068 Andres Joaquin Lopez-Contreras Danish National Research Foundatio…
Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological…
2018
Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity…
Skeletal Dysplasia Mutations Effect on Human Filamins’ Structure and Mechanosensing
2016
AbstractCells’ ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered mo…
Ancient goat genomes reveal mosaic domestication in the Fertile Crescent
2018
How humans got their goatsLittle is known regarding the location and mode of the early domestication of animals such as goats for husbandry. To investigate the history of the goat, Dalyet al.sequenced mitochondrial and nuclear sequences from ancient specimens ranging from hundreds to thousands of years in age. Multiple wild populations contributed to the origin of modern goats during the Neolithic. Over time, one mitochondrial type spread and became dominant worldwide. However, at the whole-genome level, modern goat populations are a mix of goats from different sources and provide evidence for a multilocus process of domestication in the Near East. Furthermore, the patterns described suppor…