1,721,141 research outputs found
Mutation analysis of BCR-ABL tyrosine kinase domain in new chronic phase-chronic myeloid leukemia patients with suboptimal response or treatment failure from imatinib treatment
No full textDong-Wook Kim, Dongho Kim, Soo-Hyun Kim, Hyun-Gyung Goh, Fabrizio Pane, Timothy Hughes, Gerald P. Radich, Peter Lin, Giuseppe Saglio, Susan Branford, Giovanni Martinelli, Simona Soverini and Andreas Hochhaushttp://ash.confex.com/ash/2010/webprogram/Paper34691.htm
Genomic wide microarray analysis identifies novel copy number alterations in adult acute myeloid leukemia
No full textAbstract
Introduction: Novel array-based technique as SNP microarray can detect losses or gains of chromosomic material, which could be predictive of response and can help define therapeutic strategies. The aim of this study is to improve conventional cytogenetic analysis and identify new genetic alterations relevant to leukemogenesis, by a SNP array-based genotyping approach.
Materials and Methods: We performed SNP 6.0 or Cytoscan HD (Affymetrix) in 235 Acute Myeloid Leukemia (AML) patients at diagnosis. Seventy-eight/235 samples were also performed by Whole Exome Sequencing, WES (HiSeq,Illumina). SNP Array data were analyzed by Nexus Copy Number v8.0 (BioDiscovery) and R Core Team.
Results: Copy Number Alterations (CNAs) were scattered across all chromosomes and all pts showed CNA events. SNP array analysis showed that several genes were preferentially deleted, including MRPS5 (14.8%), PHF6 (9.3%), SCAPER (7.2%), CASK (5.9%), WNK (4.6%), STAG2 (4.2%), LRRK1 (3.4%), PALB2 (3.4%), while the genes preferentially amplified were RABL2B (16.1%), NF2 (10.2%), NBPF9 (7.6%), JAK2 (6.8%), RB1, NF1 and KMT2A (4.2%), PTEN (3.4%), TP73 and SMAD2 (2.5%). Single-copy losses and deletions were enriched (p<.001) for genes mapping into the following pathways: aberrant PD-1 signaling, loss of function of SMAD4 in cancer and SMAD4 MH2 Domain mutants in cancer. The functional pathways significantly (p<.001) deregulated in our cohort with single copy gain and homozygous amplification were: regulation of transcription and nucleic acid, negative regulation of metabolic processes, constitutive signaling by aberrant PI3K in cancer and PI3K/AKT network. Finally, in order to define driver alterations, we correlate deletions and losses with mutational data. Interestingly, we found losses which are also targeted by mutations (BRCA2, LRRK1). Moreover, some deleted genes, as CASK, CDK6 and MAPT, were involved in pathways affected by genomic mutations (CASK deletion and MPP6 mutation, CDK6 deletion and PPM1D mutation, MAPT deletion and SPAG5 mutation).
Conclusion: We have identified new CNAs and pathways involving novel potential leukemia-related genes. Our results suggest that the comparison between SNP and WES data could provide important findings on prognosis of AML patients. Minimal deleted regions of genes implicated in deregulated pathways deserve further investigation in order to identify new candidate genes which could be relevant AML biomarkers. Acknowledgements: ELN,AIL,AIRC,progetto Regione-Università 2010-12 (L. Bolondi),FP7 NGS-PTL project,HARMONY.
Citation Format: Maria Chiara Fontana, Giovanni Marconi, Cristina Papayannidis, Eugenio Fonzi, Giorgia Simonetti, Antonella Padella, Anna Ferrari, Emanuela Ottaviani, Silvia Lo Monaco, Stefania Paolini, Simona Soverini, Giovanni Martinelli. Genomic wide microarray analysis identifies novel copy number alterations in adult acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2451. doi:10.1158/1538-7445.AM2017-2451</jats:p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The Wee1 Inhibitor, MK-1775, Sensitizes Leukemic Cells to Different Antineoplastic Drugs Interfering with DNA Damage Response Pathway
No full textF317L BCR-ABL1 kinase domain mutation associated with a sustained major molecular response in a CML patient on dasatinib
No full textThe disease burden in chronic myeloid leukemia (CML) is linked to the activity of its chimeric oncoprotein, the BCR-ABL1 tyrosine kinase. A recent analysis of the IRIS study showed that imatinib, the first tyrosine kinase inhibitors (TKI), resulted in impressive survival and freedom from disease progression in chronic phase patients. However, 20–30% of these patients eventually develop resistance; due largely to mutations at the ABL1 kinase domain
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
