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molecular subtyping

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https://www.readbyqxmd.com/read/29050337/comprehensive-immune-transcriptomic-analysis-in-bladder-cancer-reveals-subtype-specific-immune-gene-expression-patterns-of-prognostic-relevance
#1
Runhan Ren, Kathrin Tyryshkin, Charles H Graham, Madhuri Koti, D Robert Siemens
Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050296/reverse-phase-protein-array-identification-of-triple-negative-breast-cancer-subtypes-and-comparison-with-mrna-molecular-subtypes
#2
Hiroko Masuda, Yuan Qi, Shuying Liu, Naoki Hayashi, Takahiro Kogawa, Gabriel N Hortobagyi, Debu Tripathy, Naoto T Ueno
BACKGROUND: Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses. METHODS: We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050284/mutational-analysis-of-a-chinese-family-with-oculocutaneous-albinism-type-2
#3
Xiong Wang, Yaowu Zhu, Na Shen, Jing Peng, Chunyu Wang, Haiyi Liu, Yanjun Lu
Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation of the skin, hair, and eyes accompanied with ophthalmologic abnormalities. Molecular genetic test can confirm the diagnosis of the four subtypes of OCA (OCA1-4). Herein, we report a Chinese family with two patients affected by OCA. Mutations of TYR, OCA2, TYRP1, and SLC45A2 were examined by using PCR-sequencing. Large deletions or duplications of TYR and OCA2 were examined by Multiplex Ligation-dependent Probe Amplification (MLPA) assay...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050249/profiling-cancer-associated-genetic-alterations-and-molecular-classification-of-cancer-in-korean-gastric-cancer-patients
#4
Yoonjung Kim, Mee-Yon Cho, Juwon Kim, Sung Nam Kim, Seoung Chul Oh, Kyung-A Lee
Recently, the Cancer Genome Atlas (TCGA) Research Network and Asian Cancer Research Group provided a new classification of gastric cancer (GC) to aid the development of biomarkers for targeted therapy and predict prognosis. We studied associations between genetically aberrant profiles of cancer-related genes, environmental factors, and histopathological features in 107 paired gastric tumor-non-tumor tissue GC samples. 6.5% of our GC cases were classified as the EBV subtype, 17.8% as the MSI subtype, 43.0% as the CIN subtype, and 32...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050069/-mir-449a-is-a-potential-epigenetic-biomarker-for-wnt-subtype-of-medulloblastoma
#5
Y X Li, L W Shao, T Jiang, Y Liu, Q Chang
Objective: To identify the candidate epigenetic biomarkers of Wnt subtype of medulloblastoma(MB). Methods: MicroRNAs(miRNAs) expression array was used to detect the expression of miRNAs in MB cell lines with or without treatment by demethylation reagent. Nanostring gene expression array was used to detect the expression level of mRNA in 45 samples of primary MB. Molecular subtyping was performed based on the NanoString data. The status of methylation was confirmed by methylation specific PCR. The expression of candidate miRNA was confirmed by real-time PCR...
October 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29048555/an-architecture-for-genomics-analysis-in-a-clinical-setting-using-galaxy-and-docker
#6
W Digan, H Countouris, M Barritault, D Baudoin, P Laurent-Puig, H Blons, A Burgun, B Rance
Background: Next Generation Sequencing is used on a daily basis to perform molecular analysis to determine subtypes of disease (e.g., in cancer) and to assist in the selection of the optimal treatment. Clinical bioinformatics handles the manipulation of the data generated by the sequencer, from the generation to the analysis and interpretation. Reproducibility and traceability are crucial issues in a clinical setting. Results: We have designed an approach based on the Docker container technology and Galaxy, the popular bioinformatics analysis support open-source software...
October 18, 2017: GigaScience
https://www.readbyqxmd.com/read/29047460/computational-insights-into-the-subtype-selectivity-and-message-address-efficacy-mechanisms-of-opioid-receptors-through-jdtic-binding-and-unbinding
#7
Jian-Xin Cheng, Tao Cheng, Wei-Hua Li, Gui-Xia Liu, Wei-Liang Zhu, Yun Tang
In drug design and discovery, binding affinity and selectivity are two basic properties of a drug candidate. Opioid receptors (ORs) are the main targets of strong analgesics. Like some other class A members of G-protein-coupled receptors (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of binding activity and selectivity among opioids has deeply attracted researchers for a long time. To investigate the subtype selectivity of μ, δ and κ ORs in detail, using the κ-selective antagonist JDTic as a probe, we performed a series of computational simulations, including molecular dynamics and metadynamics, on JDTic-μ/δ/κ-OR complexes...
October 19, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29046940/gastric-cancer-immunohistochemical-classification-of-molecular-subtypes-and-their-association-with-clinicopathological-characteristics
#8
Eva-Maria Birkman, Naziha Mansuri, Samu Kurki, Annika Ålgars, Minnamaija Lintunen, Raija Ristamäki, Jari Sundström, Olli Carpén
Gastric cancer is traditionally divided into intestinal and diffuse histological subtypes, but recent molecular analyses have led to novel classification proposals based on genomic alterations. While the intestinal- and diffuse-type tumours are distinguishable from each other at the molecular level, intestinal-type tumours have more diverse molecular profile. The technology required for comprehensive molecular analysis is expensive and not applicable for routine clinical diagnostics. In this study, we have used immunohistochemistry and in situ hybridisation in molecular classification of gastric adenocarcinomas with an emphasis on the intestinal subtype...
October 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29045680/report-of-a-novel-case-of-anaplastic-olfactory-groove-meningioma-and-its-methylation-subtype
#9
Aaron Song Chuan Foo, Dominic Ti Ming Tan, Char Loo Tan, Felix Sahm, Andreas von Deimling, Tseng Tsai Yeo
We report a novel case of a World Health Organization grade 3 anaplastic meningioma arising from the olfactory groove in an 83-year-old woman. Molecular and methylation profiling confirm this lesion to be an NF2 subtype, methylation class intermediate type B meningioma. As most meningiomas in this location are indolent SMO subtype lesions, our report suggests that even though rare, aggressive NF2 subtype meningiomas can also occur along the midline anterior skull base.
October 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29045527/braf-mutant-colorectal-cancer-prognosis-treatment-and-new-perspectives
#10
E Sanz-Garcia, G Argiles, E Elez, J Tabernero
The MAPK cascade plays a crucial role in tumor cell proliferation and survival. Accumulating evidence suggests that mutations in the BRAF oncogene are not only associated with poor prognosis but also linked with less benefit when treated with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Targeting this molecular aberration has thus become a matter of particular interest in mCRC drug development. In contrast to other malignances such as BRAF mutant (mt) melanoma, efficacy observed with BRAF inhibitors in mono-therapy in mCRC is poor...
July 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045503/maintenance-therapy-following-induction-chemoimmunotherapy-in-patients-with-diffuse-large-b-cell-lymphoma-current-perspective
#11
N M Reddy, C Thieblemont
Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction. Patients and methods: Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction...
July 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045452/prospective-multicenter-french-study-evaluating-the-clinical-impact-of-the-breast-cancer-intrinsic-subtype-prosigna%C3%A2-test-in-the-management-of-early-stage-breast-cancers
#12
Delphine Hequet, Céline Callens, David Gentien, Benoit Albaud, Marie-Ange Mouret-Reynier, Coraline Dubot, Paul Cottu, Cyrille Huchon, Sonia Zilberman, Helene Berseneff, Cyril Foa, Rémy Salmon, Aurélie Roulot, Florence Lerebours, Anne Salomon, Nadeem Ghali, Pascale Morel, Qianyi Li, Anne Cayre, Jean-Marc Guinebretière, John Hornberger, Frédérique Penault-Llorca, Roman Rouzier
PURPOSE: The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results...
2017: PloS One
https://www.readbyqxmd.com/read/29044966/v1b-vasopressin-receptor-trafficking-and-signaling%C3%A2-role-of-arrestins-g-proteins-and-src-kinase
#13
Sanja Perkovska, Catherine Méjean, Mohammed Akli Ayoub, Juan Li, Floriane Hemery, Maithé Corbani, Nadine Laguette, Maria-Angeles Ventura, Hélène Orcel, Thierry Durroux, Bernard Mouillac, Christiane Mendre
The signaling pathway of G protein-coupled receptors (GPCRs) is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1b R) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of β-arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V1b R-mediated MAP Kinase pathway. Using β-arrestin 1-2 KO-MEF cells, we demonstrated that both β-arrestin 1 and 2 play a fundamental role in internalization and recycling of V1b R with a rapid and transient V1b R-β-arrestin interaction in contrast to a slow and long-lasting β-arrestin recruitment of the V2 vasopressin receptor subtype (V2 R)...
October 16, 2017: Traffic
https://www.readbyqxmd.com/read/29044863/identification-of-somatic-genetic-alterations-in-ovarian-clear-cell-carcinoma-with-next-generation-sequencing
#14
Yusuke Shibuya, Hideki Tokunaga, Sakae Saito, Kazurou Shimokawa, Fumiki Katsuoka, Li Bin, Kaname Kojima, Masao Nagasaki, Masayuki Yamamoto, Nobuo Yaegashi, Jun Yasuda
Ovarian clear cell carcinoma (OCCC) is the most refractory subtype of ovarian cancer and more prevalent in Japanese than Caucasians (25% and 5% of all ovarian cancer, respectively). The aim of this study is to discover the genomic alterations that may cause OCCC and effective molecular targets for chemotherapy. Paired genomic DNAs of 48 OCCC tissues and corresponding non-cancerous tissues were extracted from formalin-fixed, paraffin embedded specimens collected between 2007 and 2015 at Tohoku University Hospital...
October 16, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#15
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29043377/-lung-cancer-what-has-been-confirmed-in-therapy
#16
REVIEW
D F Heigener, M Reck
Metastatic non-small cell lung cancer has now been subdivided into several subtypes. The five basic principles of treatment include chemotherapy, anti-angiogenic therapy, targeted therapy, immunotherapy and early palliative care. The latter should be implemented for all patients with metastatic lung cancer. The use of the other modalities depends on the histological subtype, as well as on the immunohistochemical and molecular features of the tumor.
October 17, 2017: Der Internist
https://www.readbyqxmd.com/read/29042532/three-dimensional-context-rather-than-nls-amino-acid-sequence-determines-importin-%C3%AE-subtype-specificity-for-rcc1
#17
Rajeshwer S Sankhala, Ravi K Lokareddy, Salma Begum, Ruth A Pumroy, Richard E Gillilan, Gino Cingolani
Active nuclear import of Ran exchange factor RCC1 is mediated by importin α3. This pathway is essential to generate a gradient of RanGTP on chromatin that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Here we identify the mechanisms of importin α3 selectivity for RCC1. We find this isoform binds RCC1 with one order of magnitude higher affinity than the generic importin α1, although the two isoforms share an identical NLS-binding groove. Importin α3 uses its greater conformational flexibility to wedge the RCC1 β-propeller flanking the NLS against its lateral surface, preventing steric clashes with its Armadillo-core...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29041931/reprogramming-of-stromal-fibroblasts-by-snai2-contributes-to-tumor-desmoplasia-and-ovarian-cancer-progression
#18
Zongyuan Yang, Xin Yang, Sen Xu, Ping Jin, Xiaoting Li, Xiao Wei, Dan Liu, Kecheng Huang, Sixiang Long, Ya Wang, Chaoyang Sun, Gang Chen, Junbo Hu, Li Meng, Ding Ma, Qinglei Gao
BACKGROUND: Molecular profiling in ovarian cancer (OC) revealed that the desmoplasia subtype presented the poorest prognosis, highlighting the contribution of stromal fibroblasts in tumor progression. This study aimed to investigate the molecular characteristics of SNAI2 driving the transcriptional reprogramming of fibroblasts within tumors. METHODS: SNAI2 expression was evaluated in microdissected profiles of various cancers and in various molecular subtypes of OC...
October 17, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29040662/molecular-subtyping-of-tumors-from-patients-with-familial-glioma
#19
Vanessa Y Ruiz, Corinne E Praska, Georgina Armstrong, Thomas M Kollmeyer, Seiji Yamada, Paul A Decker, Matthew L Kosel, Jeanette E Eckel-Passow, The Gliogene Consortium, Daniel H Lachance, Matthew N Bainbridge, Beatrice S Melin, Melissa L Bondy, Robert B Jenkins
BACKGROUND: Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on IDH mutation and 1p/19q co-deletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas, and that tumors in the same family should have the same molecular subtype. METHODS: Participants in the FG study (Gliogene) provided samples for germline DNA analysis...
October 10, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29039487/functional-analysis-of-hoxa10-and-hoxb4-in-human-medulloblastoma-cell-lines
#20
Ricardo Bonfim-Silva, Fernanda Ursoli Ferreira Melo, Carolina Hassibe Thomé, Kuruvilla Joseph Abraham, Fábio Augusto Labre De Souza, Fernando Silva Ramalho, Hélio Rubens Machado, Ricardo Santos De Oliveira, Angelo A Cardoso, Dimas Tadeu Covas, Aparecida Maria Fontes
Medulloblastoma (MB) is a malignant childhood brain tumor which at molecular level is classified into at least four major subtypes: WNT, SHH, group C and group D differing in response to treatment. Previous studies have associated changes in expression levels and activation of certain HOX genes with MB development. In the present study, we investigate the role of HOX genes in two attributes acquired by tumor cells: migration and proliferation potential, as well as, in vivo tumorigenic potential. We analyzed UW402, UW473, DAOY and ONS-76 human pediatric MB cell lines and cerebellum primary cultures...
October 10, 2017: International Journal of Oncology
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