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About 55,058 results

Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191900
The New England Journal of Medicine; Roberts KG, Li Y et. al.

Sep 10th, 2014 - Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and ad...

Integrated analysis of somatic mutations and focal copy-number changes identifies key g...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819251
Nature Genetics; Guichard C, Amaddeo G et. al.

May 8th, 2012 - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2)...

Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced...
https://doi.org/10.1002/cncr.24438
Cancer Figlin RA, de Souza P et. al.

Jun 15th, 2009 - Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to determine if baseline levels of the tumor molecular markers PTEN and HIF1 alpha correlated with efficacy in patients treated with temsirolimus (Torisel) versus interferon-alpha (IFN). Patients in the IFN group received 3 million U (MU) subcutaneously 3x weekly, escalating to 18 MU....

Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
https://doi.org/10.1038/ng.2599
Nature Genetics; Dibbens LM, de Vries B et. al.

Apr 1st, 2013 - The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) ...

The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem h...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056452
Nature Genetics; Wu G, Diaz AK et. al.

Apr 7th, 2014 - Pediatric high-grade glioma (HGG) is a devastating disease with a less than 20% survival rate 2 years after diagnosis. We analyzed 127 pediatric HGGs, including diffuse intrinsic pontine gliomas (DIPGs) and non-brainstem HGGs (NBS-HGGs), by whole-genome, whole-exome and/or transcriptome sequencing. We identified recurrent somatic mutations in ACVR1 exclusively in DIPGs (32%), in addition to pre...

Copy number variation analysis in 98 individuals with PHACE syndrome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971866
The Journal of Investigative Dermatology; Siegel DH, Shieh JTC et. al.

Oct 25th, 2012 - PHACE syndrome is the association of large segmental facial hemangiomas and congenital anomalies, such as posterior fossa malformations, cerebral arterial anomalies, coarctation of the aorta, eye anomalies, and sternal defects. To date, the reported cases of PHACE syndrome have been sporadic, suggesting that PHACE may have a complex pathogenesis. We report here genomic copy number variation (CN...

Early-onset inflammatory bowel disease and common variable immunodeficiency-like diseas...
https://doi.org/10.1016/j.jaci.2014.02.034
The Journal of Allergy and Clinical Immunology; Salzer E, Kansu A et. al.

Apr 21st, 2014 - Alterations of immune homeostasis in the gut can result in development of inflammatory bowel disease (IBD). Recently, Mendelian forms of IBD have been discovered, as exemplified by deficiency of IL-10 or its receptor subunits. In addition, other types of primary immunodeficiency disorders might be associated with intestinal inflammation as one of their leading clinical presentations. We investi...

Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components ...
https://doi.org/10.1038/ng.1014
Nature Genetics; Guo G, Gui Y et. al.

Dec 5th, 2011 - We sequenced whole exomes of ten clear cell renal cell carcinomas (ccRCCs) and performed a screen of ∼1,100 genes in 88 additional ccRCCs, from which we discovered 12 previously unidentified genes mutated at elevated frequencies in ccRCC. Notably, we detected frequent mutations in the ubiquitin-mediated proteolysis pathway (UMPP), and alterations in the UMPP were significantly associated with o...

Pathogenesis of bone disease in multiple myeloma: from bench to bedside.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802524
Blood Cancer Journal; Terpos E, Ntanasis-Stathopoulos I et. al.

Jan 13th, 2018 - Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of...

Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma.
https://doi.org/10.1111/j.1365-2141.2012.09113.x
British Journal of Haematology; Otto C, Giefing M et. al.

Apr 3rd, 2012 - Hodgkin and Reed/Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) show constitutive activation of nuclear factor (NF)-κB. Several genetic lesions contribute to this deregulated NF-κB activity. Here, we analysed two further NF-κB regulators for genetic lesions, the inhibitory factor TRAF3 and the key signalling component of the alternative NF-κB pathway, MAP3K14 (NIK). Single nucleotide...

Neutral antibodies to the TSH receptor are present in Graves' disease and regulate sele...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954721
Endocrinology Morshed SA, Ando T et. al.

Sep 16th, 2010 - TSH receptor (TSHR) antibodies (Abs) may be stimulating, blocking, or neutral in their functional influences and are found in patients with autoimmune thyroid disease, especially Graves' disease (GD). Stimulators are known to activate the thyroid epithelial cells via both Gs- and Gq-coupled signaling pathways, whereas blockers inhibit the action of TSH and may act as weak agonists. However, TSH...

BRAF mutation status in gastrointestinal stromal tumors.
https://doi.org/10.1309/AJCPPCKGA2QGBJ1R
American Journal of Clinical Pathology; Hostein I, Faur N et. al.

Dec 21st, 2009 - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors characterized by mutations of KIT or PDGFRA. The objectives of this study were to evaluate BRAF mutations in GISTs and then to correlate BRAF mutational status in the tumor with clinical parameters, with B-raf expression, and with activation of some cellular pathways. BRAF mutation was screened in 321 GISTs with 70 wild-type GISTs. ...

Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: molecular c...
https://doi.org/10.1111/j.1365-2141.2007.06958.x
British Journal of Haematology; Niemeyer CM, Kratz CP

Feb 27th, 2008 - Myelodysplastic syndromes (MDS) and the mixed myelodysplastic/myeloproliferative disorder juvenile myelomonocytic leukaemia (JMML) are rare haematopoietic stem cell diseases in children. While MDS-initiating events remain largely obscure, a growing body of clinical, genetic and laboratory evidence suggests that JMML is, at least in part, caused by aberrant signal transduction resulting from mut...

Targeting BRAF in pediatric brain tumors.
https://doi.org/10.14694/EdBook_AM.2014.34.e436
American Society of Clinical Oncology Educational Book. A... Kieran MW

May 26th, 2014 - The role of BRAF in adult malignancy has been well documented over the last decade and recent data have extended these findings to a number of pediatric cancers. In this and the accompanying articles, we will review the importance of the BRAF pathway in signal transduction resulting in cell proliferation, migration, differentiation, and angiogenesis with a focus on three major pediatric disease...

Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904512
Cancer Cell; Gregory MA, Phang TL et. al.

Jul 8th, 2010 - Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to eradicate Bcr-Abl(+) leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl(+) leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib mesylate in CML cells. This screen identified numerous compone...

Oncogenic mutations of ALK kinase in neuroblastoma.
https://doi.org/10.1038/nature07399
Nature Chen Y, Takita J et. al.

Oct 16th, 2008 - Neuroblastoma in advanced stages is one of the most intractable paediatric cancers, even with recent therapeutic advances. Neuroblastoma harbours a variety of genetic changes, including a high frequency of MYCN amplification, loss of heterozygosity at 1p36 and 11q, and gain of genetic material from 17q, all of which have been implicated in the pathogenesis of neuroblastoma. However, the scarcit...

From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of am...
https://doi.org/10.1038/ng.557
Nature Genetics; Lincecum JM, Vieira FG et. al.

Mar 29th, 2010 - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Using unbiased transcript profiling in an ALS mouse model, we identified a role for the co-stimulatory pathway, a key regulator of immune responses. Furthermore, we observed that this pathway is upregulated in the blood of 56% of human patients with ALS. A therapy using a...

BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.
https://doi.org/10.1038/nchembio.775
Nature Chemical Biology; Hantschel O, Warsch W et. al.

Jan 30th, 2012 - Constitutive activation of STAT5 is critical for the maintenance of chronic myeloid leukemia (CML) characterized by the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (TKIs) for the STAT5-activating kinase JAK2 have been discussed as a treatment option for CML patients. Using murine leukemia models combined with inducible ablation of JAK2, we show JAK2 dependence for initial lymphoid transform...

Functional correction of type VII collagen expression in dystrophic epidermolysis bullosa.
https://doi.org/10.1038/jid.2010.249
The Journal of Investigative Dermatology; Murauer EM, Gache Y et. al.

Aug 19th, 2010 - Functional defects in type VII collagen, caused by premature termination codons on both alleles of the COL7A1 gene, are responsible for the severe autosomal recessive types of the skin blistering disease, recessive dystrophic epidermolysis bullosa (RDEB). The full-length COL7A1 complementary DNA (cDNA) is about 9 kb, a size that is hardly accommodated by therapeutically used retroviral vectors....

New insights into the pathogenesis of adenosine deaminase-severe combined immunodeficie...
https://doi.org/10.1097/ACI.0b013e3283327da5
Current Opinion in Allergy and Clinical Immunology; Sauer AV, Aiuti A

Sep 25th, 2009 - Adenosine deaminase (ADA)- deficient severe combined immunodeficiency (SCID) is a complex metabolic and immunological disorder, characterized by a severe immunodeficiency due to the accumulation of purine metabolites in plasma and cells. This review summarizes recent findings on the pathogenesis of immunological and nonimmunological defects in ADA deficiency and the successful outcome of gene t...