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https://www.readbyqxmd.com/read/27915062/rosette-forming-glioneuronal-tumor-originating-from-the-spinal-cord-report-of-two-cases-and-literature-review
#1
Lian Duan, Yunkun Zhang, Weilun Fu, Sumin Geng
Rosette-forming glioneuronal tumor (RGNT) is a recently recognized and rarely encountered tumor occurring in the fourth ventricle. Histologically, it is composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a neurocytic component forming neurocytic rosettes and/or perivascular rosettes. The authors describe two extremely rare cases of RGNT arising from the spinal cord, which were misdiagnosed as ependymoma and astrocytoma preoperatively. Symptoms included dissociated sensory disturbance, episodic pain and fatigue, as well as motor disturbance, had been presented for two years and two months, respectively...
November 30, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27913526/update-from-the-latest-who-classification-of-mpns-a-user-s-manual
#2
Francesco Passamonti, Margherita Maffioli
The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913435/idh2-mutations-define-a-unique-subtype-of-breast-cancer-with-altered-nuclear-polarity
#3
Sarah Chiang, Britta Weigelt, Huei-Chi Wen, Fresia Pareja, Ashwini Raghavendra, Luciano G Martelotto, Kathleen A Burke, Thais Basili, Anqi Li, Felipe C Geyer, Salvatore Piscuoglio, Charlotte K Y Ng, Achim A Jungbluth, Jörg Balss, Stefan Pusch, Gabrielle M Baker, Kimberly S Cole, Andreas von Deimling, Julie M Batten, Jonathan D Marotti, Hwei-Choo Soh, Benjamin L McCalip, Jonathan Serrano, Raymond S Lim, Kalliopi P Siziopikou, Song Lu, Xiaolong Liu, Tarek Hammour, Edi Brogi, Matija Snuderl, A John Iafrate, Jorge S Reis-Filho, Stuart J Schnitt
Solid papillary carcinoma with reverse polarity (SPCRP) is a rare breast cancer subtype with an obscure etiology. In this study, we sought to describe its unique histopathologic features and to identify the genetic alterations that underpin SPCRP using massively parallel whole-exome and targeted sequencing. The morphologic and immunohistochemical features of SPCRP support the invasive nature of this subtype. Ten of 13 (77%) SPCRPs harbored hotspot mutations at R172 of the isocitrate dehydrogenase IDH2, of which 8 of 10 displayed concurrent pathogenic mutations affecting PIK3CA or PIK3R1 One of the IDH2 wild-type SPCRPs harbored a TET2 Q548* truncating mutation coupled with a PIK3CA H1047R hotspot mutation...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27904447/long-term-survival-in-glioblastoma-methyl-guanine-methyl-transferase-mgmt-promoter-methylation-as-independent-favourable-prognostic-factor
#4
Uros Smrdel, Mara Popovic, Matjaz Zwitter, Emanuela Bostjancic, Andrej Zupan, Viljem Kovac, Damjan Glavac, Drago Bokal, Janja Jerebic
BACKGROUND: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. PATIENTS AND METHODS: Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27904446/somatic-mutations-of-isocitrate-dehydrogenases-1-and-2-are-prognostic-and-follow-up-markers-in-patients-with-acute-myeloid-leukaemia-with-normal-karyotype
#5
Marijana Virijevic, Teodora Karan-Djurasevic, Irena Marjanovic, Natasa Tosic, Mirjana Mitrovic, Irena Djunic, Natasa Colovic, Ana Vidovic, Nada Suvajdzic-Vukovic, Dragica Tomin, Sonja Pavlovic
BACKGROUND: Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. PATIENTS AND METHODS: In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27821630/mitochondrial-nadp-dependent-isocitrate-dehydrogenase-deficiency-exacerbates-mitochondrial-and-cell-damage-after-kidney-ischemia-reperfusion-injury
#6
Sang Jun Han, Hee-Seong Jang, Mi Ra Noh, Jinu Kim, Min Jung Kong, Jee In Kim, Jeen-Woo Park, Kwon Moo Park
Mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R...
November 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27821287/combination-of-rna-and-exome-sequencing-increasing-specificity-for-identification-of-somatic-point-mutations-and-indels-in-acute-leukaemia
#7
Marcus C Hansen, Laura L Herborg, Maria Hansen, Anne S Roug, Peter Hokland
Handling of large data sets from whole exome sequencing is a challenge, not the least because of the high risk of detecting false positive variants. Furthermore, there is still no consensus regarding what stage filtering of variants is performed in the bioinformatics pipeline to produce consistent result sets, the extent of filtering and how this is most optimal performed. We hypothesized that combination of coding transcriptome and exomes enables precise identification of both somatic single nucleotide and indel variants early in the bioinformatics process, superseding the need for extensive annotation and validation from external databases...
December 2016: Leukemia Research
https://www.readbyqxmd.com/read/27806376/single-cell-rna-seq-supports-a-developmental-hierarchy-in-human-oligodendroglioma
#8
Itay Tirosh, Andrew S Venteicher, Christine Hebert, Leah E Escalante, Anoop P Patel, Keren Yizhak, Jonathan M Fisher, Christopher Rodman, Christopher Mount, Mariella G Filbin, Cyril Neftel, Niyati Desai, Jackson Nyman, Benjamin Izar, Christina C Luo, Joshua M Francis, Aanand A Patel, Maristela L Onozato, Nicolo Riggi, Kenneth J Livak, Dave Gennert, Rahul Satija, Brian V Nahed, William T Curry, Robert L Martuza, Ravindra Mylvaganam, A John Iafrate, Matthew P Frosch, Todd R Golub, Miguel N Rivera, Gad Getz, Orit Rozenblatt-Rosen, Daniel P Cahill, Michelle Monje, Bradley E Bernstein, David N Louis, Aviv Regev, Mario L Suvà
Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures...
November 2, 2016: Nature
https://www.readbyqxmd.com/read/27806325/inhibiting-glutaminase-in-acute-myeloid-leukemia-metabolic-dependency-of-selected-aml-subtypes
#9
Polina Matre, Juliana Velez, Rodrigo Jacamo, Yuan Qi, Xiaoping Su, Tianyu Cai, Steven M Chan, Alessia Lodi, Shannon R Sweeney, Helen Ma, Richard Eric Davis, Natalia Baran, Torsten Haferlach, Xiaohua Su, Elsa Renee Flores, Doriann Gonzalez, Sergej Konoplev, Ismael Samudio, Courtney DiNardo, Ravi Majeti, Aaron D Schimmer, Weiqun Li, Taotao Wang, Stefano Tiziani, Marina Konopleva
Metabolic reprogramming has been described as a hallmark of transformed cancer cells. In this study, we examined the role of the glutamine (Gln) utilization pathway in acute myeloid leukemia (AML) cell lines and primary AML samples. Our results indicate that a subset of AML cell lines is sensitive to Gln deprivation. Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of Gln to glutamate. One of the two GLS isoenzymes, GLS1 is highly expressed in cancer and encodes two different isoforms: kidney (KGA) and glutaminase C (GAC)...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27781423/malignant-glioma-with-primitive-neuroectodermal-tumor-like-component-mg-pnet-novel-microarray-findings-in-a-pediatric-patient
#10
Jinglan Liu, Matthew P Keisling, Ayman Samkari, Gregory Halligan, Judy M Pascasio, Christos D Katsetos
Central nervous system (CNS) tumors exhibiting dual features of malignant glioma (MG) and primitive neuroectodermal tumor (PNET) are rare and diagnostically challenging. Previous studies have shown that MG-PNET carry MYCN or MYC gene amplifications within the PNET component concomitant with glioma-associated alterations, most commonly 10q loss, in both components [9]. Here we confirm and extend the profile of molecular genetic findings in a MG-PNET involving the left frontal lobe of a 12-year-old male. Histologically, the PNET-like component showed morphological features akin to anaplastic medulloblastoma highlighted by widespread immunoreactivity for βIII-tubulin (TUBB3) and nonphosphorylated neurofilament protein, and to a lesser degree, Neu-N, synaptophysin, and CD99, whereas the gliomatous component was demarcated by glial fibrillary acidic protein (GFAP) labeling...
October 26, 2016: Clinical Neuropathology
https://www.readbyqxmd.com/read/27780605/idh1-2-gene-hotspot-mutations-in-central-nervous-system-tumours-analysis-of-922-chinese-patients
#11
Ni Chen, Tianpin Yu, Jing Gong, Ling Nie, Xueqin Chen, Mengni Zhang, Miao Xu, Junya Tan, Zhengzheng Su, Jinjing Zhong, Qiao Zhou
Mutations of isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes have been identified as early molecular events in the development of astrocytomas and oligodendrogliomas. Data regarding the status and prevalence of IDH1/2 mutations in Chinese patients are limited. Herein we report our data from West China Hospital, a major Chinese medical centre. IDH1(R132H) mutation was analysed by immunohistochemistry with the mutation-specific IDH1(R132H) antibody in 1011 patients, including 922 central nervous system (CNS) tumours and 89 non-neoplastic CNS lesions, and PCR-based direct sequencing of IDH1/2 gene mutation in 570 of these samples...
October 22, 2016: Pathology
https://www.readbyqxmd.com/read/27759701/concomitant-cutaneous-langerhans-cell-hystiocytosis-and-leukemia-cutis
#12
Sergio Pina-Oviedo, Carlos A Torres-Cabala, Roberto N Miranda, Michael T Tetzlaff, Selina Singh, Ronald P Rapini, Victor G Prieto, Phyu P Aung
Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 10/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis...
October 18, 2016: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/27721426/isocitrate-dehydrogenase-mutations-in-myeloid-malignancies
#13
B C Medeiros, A T Fathi, C D DiNardo, D A Pollyea, S M Chan, R Swords
Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). IDH proteins are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation, and DNA modification. The IDH2 protein is localized in the mitochondria and is a critical component of the tricarboxylic acid (TCA, also called the 'citric acid' or Krebs) cycle...
October 10, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27686946/temozolomide-chemotherapy-versus-radiotherapy-in-high-risk-low-grade-glioma-eortc-22033-26033-a-randomised-open-label-phase-3-intergroup-study
#14
Brigitta G Baumert, Monika E Hegi, Martin J van den Bent, Andreas von Deimling, Thierry Gorlia, Khê Hoang-Xuan, Alba A Brandes, Guy Kantor, Martin J B Taphoorn, Mohamed Ben Hassel, Christian Hartmann, Gail Ryan, David Capper, Johan M Kros, Sebastian Kurscheid, Wolfgang Wick, Roelien Enting, Michele Reni, Brian Thiessen, Frederic Dhermain, Jacoline E Bromberg, Loic Feuvret, Jaap C Reijneveld, Olivier Chinot, Johanna M M Gijtenbeek, John P Rossiter, Nicolas Dif, Carmen Balana, Jose Bravo-Marques, Paul M Clement, Christine Marosi, Tzahala Tzuk-Shina, Robert A Nordal, Jeremy Rees, Denis Lacombe, Warren P Mason, Roger Stupp
BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged >40 years, progressive disease, tumour size >5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration...
November 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27649069/a-new-functional-idh2-genetic-variant-is-associated-with-the-risk-of-lung-cancer
#15
Jiangjiang Li, Jingchen Lu, Ya He, Yong Wu, Yuan Wu, Xin Song, Yuee Jiang, Min Tang, Xinxian Weng, Wei Yi, Xiangjian Luo, Lunquan Sun, Ann M Bode, Ya Cao
Recently, mutations in isocitrate dehydrogenase 1/2 (IDH1/2) were discovered in 70% of low-grade glioma and secondary glioblastoma multiforme. The discovery of an oncogenic function and the identification of onco-metabolites of IDH1/2 support new roles for metabolism in cancer. For example, some evidence indicates that IDH2 might also exhibit oncogenic functions by promoting cellular metabolism and cancer cell growth. We examined the association between IDH2 rs11540478 and lung cancer risk in 262 lung cancer patient cases and 602 healthy control subjects and also investigated the biological function of rs11540478 in vivo...
September 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27621679/idh1-and-idh2-mutations-as-novel-therapeutic-targets-current-perspectives
#16
REVIEW
Johanna Mondesir, Christophe Willekens, Mehdi Touat, Stéphane de Botton
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies. Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in the accumulation and secretion in vast excess of an oncometabolite, the D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis...
2016: Journal of Blood Medicine
https://www.readbyqxmd.com/read/27595804/immunohistochemistry-using-monoclonal-antibody-msmab-2-is-useful-to-detect-idh1-r132l-in-intrahepatic-cholangiocarcinoma
#17
Akimasa Hayashi, Kento Misumi, Junji Shibahara, Norihiro Kokudo, Yukinari Kato, Masashi Fukayama
Immunohistochemical analysis using specific antibodies is a useful and convenient method to detect proteins altered by somatic mutations. We previously generated the rat monoclonal antibody MsMab-2, which recognizes isocitrate dehydrogenase (IDH)1 R132L and IDH2 R172M. In the present study, we used an immunohistochemical method to examine MsMab-2 immunoreactivity in 95 cases of intrahepatic cholangiocarcinoma, including five IDH1 R132L and one IDH2 R172M mutant cases confirmed by direct sequencing. Tissue microarray section slides of all IDH1/2-mutant and wild-type cases, as well as whole section slides of IDH1 R132L and IDH2 R172M cases were immunostained using an autostainer...
October 2016: Pathology International
https://www.readbyqxmd.com/read/27591990/familial-hematological-malignancies-new-idh2-mutation
#18
Walid-Sabri Hamadou, Violaine Bourdon, Sébastien Létard, Fabienne Brenet, Sofien Laarif, Sawsen Besbes, Angelo Paci, Muriel David, Virginie Penard-Lacronique, Yosra Ben Youssef, Mohamed-Adnène Laatiri, François Eisinger, Véronique Mari, Paul Gesta, Hélène Dreyfus, Valérie Bonadona, Catherine Dugast, Hélène Zattara, Laurence Faivre, Testsuro Noguchi, Abderrahim Khélif, Chaker Ben Salem, Patrice Dubreuil, Hagay Sobol, Zohra Soua
Isocitrate dehydrogenase IDH 1 and IDH 2 mutations were reported in several cancer forms, especially in hematological malignancies, but were never been investigated in familial aggregation. The aim of this study is to determine whether germline isocitrate dehydrogenase genes mutations are involved.We targeted IDH1 and IDH2 genes in 104 familial cases belonging to Tunisian and French populations, including several forms of hematological malignancies and cosegregated solid tumors.We report one IDH1 variant: c...
September 3, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27582470/oncometabolite-d-2-hydroxyglutarate-impairs-%C3%AE-ketoglutarate-dehydrogenase-and-contractile-function-in-rodent-heart
#19
Anja Karlstaedt, Xiaotian Zhang, Heidi Vitrac, Romain Harmancey, Hernan Vasquez, Jing Han Wang, Margaret A Goodell, Heinrich Taegtmeyer
Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27577048/the-oncometabolite-r-2-hydroxyglutarate-activates-nf-%C3%AE%C2%BAb-dependent-tumor-promoting-stromal-niche-for-acute-myeloid-leukemia-cells
#20
Jing-Yi Chen, You-Syuan Lai, Hui-Jen Tsai, Cheng-Chin Kuo, B Linju Yen, Su-Peng Yeh, H Sunny Sun, Wen-Chun Hung
Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue...
2016: Scientific Reports
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