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Pediatric brain cancer

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https://www.readbyqxmd.com/read/28104717/clinical-targeted-exome-based-sequencing-in-combination-with-genome-wide-copy-number-profiling-precision-medicine-analysis-of-203-pediatric-brain-tumors
#1
Shakti H Ramkissoon, Pratiti Bandopadhayay, Jaeho Hwang, Lori A Ramkissoon, Noah F Greenwald, Steven E Schumacher, Ryan O'Rourke, Nathan Pinches, Patricia Ho, Hayley Malkin, Claire Sinai, Mariella Filbin, Ashley Plant, Wenya Linda Bi, Michael S Chang, Edward Yang, Karen D Wright, Peter E Manley, Matthew Ducar, Sanda Alexandrescu, Hart Lidov, Ivana Delalle, Liliana C Goumnerova, Alanna J Church, Katherine A Janeway, Marian H Harris, Laura E MacConaill, Rebecca D Folkerth, Neal I Lindeman, Charles D Stiles, Mark W Kieran, Azra H Ligon, Sandro Santagata, Adrian M Dubuc, Susan N Chi, Rameen Beroukhim, Keith L Ligon
BACKGROUND: Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established. METHODS: Profile is an institution-wide prospective clinical research initiative that uses targeted sequencing to identify targetable alterations in tumors. OncoPanel, a multiplexed targeted exome-sequencing platform that includes 300 cancer-causing genes, was used to assess single nucleotide variants and rearrangements/indels...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28094001/autophagy-inhibition-overcomes-multiple-mechanisms-of-resistance-to-braf-inhibition-in-brain-tumors
#2
Jean M Mulcahy Levy, Shadi Zahedi, Andrea M Griesinger, Andrew Morin, Kurtis D Davies, Dara L Aisner, B K Kleinschmidt-DeMasters, Brent E Fitzwalter, Megan L Goodall, Jacqueline Thorburn, Vladimir Amani, Andrew M Donson, Diane K Birks, David M Mirsky, Todd C Hankinson, Michael H Handler, Adam L Green, Rajeev Vibhakar, Nicholas K Foreman, Andrew Thorburn
Kinase inhibitors are effective cancer therapies, but tumors frequently develop resistance. Current strategies to circumvent resistance target the same or parallel pathways. We report here that targeting a completely different process, autophagy, can overcome multiple BRAF inhibitor resistance mechanisms in brain tumors. BRAF(V600E)mutations occur in many pediatric brain tumors. We previously reported that these tumors are autophagy-dependent and a patient was successfully treated with the autophagy inhibitor chloroquine after failure of the BRAF(V600E) inhibitor vemurafenib, suggesting autophagy inhibition overcame the kinase inhibitor resistance...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28069802/genomic-profiling-of-a-large-set-of-diverse-pediatric-cancers-identifies-known-and-novel-mutations-across-tumor-spectra
#3
Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M Frampton, James X Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L Erlich, Jeffrey S Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A Miller, Philip J Stephens, Katherine A Janeway, John M Maris, Soheil Meshinchi, Trevor J Pugh, Jack F Shern, Doron Lipson
Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28068559/the-ageing-genome-clonal-mosaicism-and-chronic-disease
#4
REVIEW
Mitchell J Machiela, Stephen J Chanock
Clonal mosaicism arises when a postzygotic mutational event is detectable in subpopulations of cells as an alternative genotype while not present in the germline genome. Although described in a subset of pediatric disorders, new genomic technologies have detected higher than anticipated frequencies of clonal mosaicism in adult population studies, stimulating investigation as to how clonal mosaicism could contribute to chronic human diseases, such as cancer, diabetes and neurodegenerative disorders. It has also been postulated to be an important mechanism for functional cellular diversity, including the brain...
January 6, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28059591/epigenetic-modification-in-chromatin-machinery-and-its-deregulation-in-pediatric-brain-tumors-insight-into-epigenetic-therapies
#5
Eleonore Maury, Rintaro Hashizume
Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28052939/no-association-between-radiation-dose-from-pediatric-ct-scans-and-risk-of-subsequent-hodgkin-lymphoma
#6
Amy Berrington de Gonzalez, Neige Journy, Choonsik Lee, Lindsay M Morton, Richard Harbron, Douglas R Stewart, Louise Parker, Alan W Craft, Kieran McHugh, Mark Little, Mark Pearce
BACKGROUND: We examined the relationship between estimated radiation dose from CT scans and subsequent Hodgkin lymphoma in the UK pediatric CT scans cohort. METHODS: A retrospective, record linkage cohort included patients aged 0-21 years who underwent CT scans between 1980 and 2002 and were followed up for cancer or death until 2008. Poisson regression analysis was used to evaluate the relationship between estimated radiation dose (lagged by two years) and incident Hodgkin lymphoma diagnosed at least two years after the first CT scan...
January 4, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28046705/su-f-t-202-an-evaluation-method-of-lifetime-attributable-risk-for-comparing-between-proton-beam-therapy-and-intensity-modulated-x-ray-therapy-for-pediatric-cancer-patients-by-averaging-four-dose-response-models-for-carcinoma-induction
#7
M Tamura, Y Ito, H Sakurai, M Mizumoto, S Kamizawa, S Murayama, H Yamashita, S Takao, R Suzuki, H Shirato
PURPOSE: To examine how much lifetime attributable risk (LAR) as an in silico surrogate marker of radiation-induced secondary cancer would be lowered by using proton beam therapy (PBT) in place of intensity modulated x-ray therapy (IMXT) in pediatric patients. METHODS: From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: a) brain, head, and neck, b) thoracic, c) abdominal, and d) whole craniospinal (WCNS) irradiation...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28044936/nano-delivery-in-pediatric-tumors-looking-back-moving-forward
#8
Marta Colletti, Virginia Di Paolo, Angela Galardi, Giuseppe Maria Milano, Angela Mastronuzzi, Franco Locatelli, Angela Di Giannatale
Recent advances in the treatment of pediatric tumors led to an improvement of survival in this population. As a result, many pediatric survivors experience long-term effects that impact their quality of life. Therefore, it is extremely important to identify new treatment approaches that may target the tumor minimizing the drug-related side effects. Over the past 10 years, remarkable advances in nanomedicine have provided several potential tools for cancer treatment. Recently, there has been a growing interest towards therapeutic nanocarriers in the pediatric field, since they represent a new strategy to enhance the drug efficacy and reduce the toxicity...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28017613/developmental-regulation-of-mitochondrial-apoptosis-by-c-myc-governs-age-and-tissue-specific-sensitivity-to-cancer-therapeutics
#9
Kristopher A Sarosiek, Cameron Fraser, Nathiya Muthalagu, Patrick D Bhola, Weiting Chang, Samuel K McBrayer, Adam Cantlon, Sudeshna Fisch, Gail Golomb-Mello, Jeremy A Ryan, Jing Deng, Brian Jian, Chris Corbett, Marti Goldenberg, Joseph R Madsen, Ronglih Liao, Dominic Walsh, John Sedivy, Daniel J Murphy, Daniel Ruben Carrasco, Shenandoah Robinson, Javid Moslehi, Anthony Letai
It is not understood why healthy tissues can exhibit varying levels of sensitivity to the same toxic stimuli. Using BH3 profiling, we find that mitochondria of many adult somatic tissues, including brain, heart, and kidneys, are profoundly refractory to pro-apoptotic signaling, leading to cellular resistance to cytotoxic chemotherapies and ionizing radiation. In contrast, mitochondria from these tissues in young mice and humans are primed for apoptosis, predisposing them to undergo cell death in response to genotoxic damage...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28017579/seizures-caused-by-brain-tumors-in-children
#10
Iván Sánchez Fernández, Tobias Loddenkemper
PURPOSE: To review the epidemiology, clinical features, and treatment of seizures secondary to pediatric brain tumors. METHOD: Literature review. RESULTS: Pediatric brain tumors are the most common solid pediatric tumor and the most common cause of death in pediatric cancer. Seizures are one of the most common symptoms of pediatric brain tumors. Factors associated with increased risk of seizures include supratentorial location, gray matter involvement, low-grade, and certain histological features-especially dysembryoplastic neuroepithelial tumor, ganglioglioma, and oligodendroglioma...
December 7, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28004469/long-term-follow-up-after-proton-beam-therapy-for-pediatric-tumors-a-japanese-national-survey
#11
Masashi Mizumoto, Shigeyuki Murayama, Tetsuo Akimoto, Yusuke Demizu, Takashi Fukushima, Yuji Ishida, Yoshiko Oshiro, Haruko Numajiri, Hiroshi Fuji, Toshiyuki Okumura, Hiroki Shirato, Sakurai Hideyuki
Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0-19 years) at the time of treatment...
December 22, 2016: Cancer Science
https://www.readbyqxmd.com/read/27978785/the-five-pediatric-cancers-update-on-genetic-implications
#12
Stacy Cooper, Jeffrey Rubens, Joann Bodurtha
Pediatric cancer has undergone significant improvements in survival over the past several decades, in part due to a better understanding of the underlying genetic aberrations of each oncologic diagnosis, which has allowed for more effective targeted therapies. Pediatric brain tumors, leukemia, lymphoma, Wilms tumor, and retinoblastoma are exemplary pediatric cancers that each have specific epidemiology regarding children at risk as well as characteristic associated genetic lesions. These genetic features are more commonly being used to provide risk stratification, as well as to identify novel pathways for targeted therapy...
December 13, 2016: Current Pediatric Reviews
https://www.readbyqxmd.com/read/27978508/targeted-next-generation-sequencing-of-pediatric-neuro-oncology-patients-improves-diagnosis-identifies-pathogenic-germline-mutations-and-directs-targeted-therapy
#13
Cassie N Kline, Nancy M Joseph, James P Grenert, Jessica van Ziffle, Eric Talevich, Courtney Onodera, Mariam Aboian, Soonmee Cha, David R Raleigh, Steve Braunstein, Joseph Torkildson, David Samuel, Michelle Bloomer, Alejandra G de Alba Campomanes, Anuradha Banerjee, Nicholas Butowski, Corey Raffel, Tarik Tihan, Andrew W Bollen, Joanna J Phillips, W Michael Korn, Iwei Yeh, Boris C Bastian, Nalin Gupta, Sabine Mueller, Arie Perry, Theodore Nicolaides, David A Solomon
BACKGROUND: Molecular profiling is revolutionizing cancer diagnostics and leading to personalized therapeutic approaches. Herein we describe our clinical experience performing targeted sequencing for 31 pediatric neuro-oncology patients. METHODS: We sequenced 510 cancer-associated genes from tumor and peripheral blood to identify germline and somatic mutations, structural variants, and copy number changes. RESULTS: Genomic profiling was performed on 31 patients with tumors including 11 high-grade gliomas, 8 medulloblastomas, 6 low-grade gliomas, 1 embryonal tumor with multilayered rosettes, 1 pineoblastoma, 1 uveal ganglioneuroma, 1 choroid plexus carcinoma, 1 chordoma, and 1 high-grade neuroepithelial tumor...
November 14, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27956195/albumin-nanoparticles-for-glutathione-responsive-release-of-cisplatin-new-opportunities-for-medulloblastoma
#14
Giuseppina Catanzaro, Manuela Curcio, Giuseppe Cirillo, Umile Gianfranco Spizzirri, Zein Mersini Besharat, Luana Abballe, Alessandra Vacca, Francesca Iemma, Nevio Picci, Elisabetta Ferretti
Redox-responsive nanoparticles were synthesized by desolvation of bovine serum albumin followed by disulfide-bond crosslinking with N, N'-Bis (acryloyl) cystamine. Dynamic light scattering and transmission electron microscopy studies revealed spherical nanoparticles (mean diameter: 83nm, polydispersity index: 0.3) that were glutathione-responsive. Confocal microscopy revealed rapid, efficient internalization of the nanoparticles by Daoy medulloblastoma cells and healthy controls (HaCaT keratinocytes). Cisplatin-loaded nanoparticles with drug:carrier ratios of 5%, 10%, and 20% were tested in both cell lines...
December 9, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27941797/smarcb1-mediated-swi-snf-complex-function-is-essential-for-enhancer-regulation
#15
Xiaofeng Wang, Ryan S Lee, Burak H Alver, Jeffrey R Haswell, Su Wang, Jakub Mieczkowski, Yotam Drier, Shawn M Gillespie, Tenley C Archer, Jennifer N Wu, Evgeni P Tzvetkov, Emma C Troisi, Scott L Pomeroy, Jaclyn A Biegel, Michael Y Tolstorukov, Bradley E Bernstein, Peter J Park, Charles W M Roberts
SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers...
December 12, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27926496/the-therapeutic-potential-of-targeting-the-pi3k-pathway-in-pediatric-brain-tumors
#16
REVIEW
Hazel A Rogers, Jasper Estranero, Keshni Gudka, Richard G Grundy
Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27917595/societal-preferences-in-the-treatment-of-pediatric-medulloblastoma-balancing-risk-of-death-and-quality-of-life
#17
Amir Khakban, Tima Mohammadi, Larry D Lynd, Don Mabbott, Eric Bouffet, Louise Gastonguay, Zafar Zafari, David Malkin, Michael Taylor, Carlo A Marra
PURPOSE: Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence...
December 4, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27899404/tapping-big-data-to-help-little-patients
#18
(no author information available yet)
Through a large-scale tumor-sequencing effort for pediatric brain cancer, researchers hope to bring personalized care to young patients.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27893452/confounding-of-the-association-between-radiation-exposure-from-ct-scans-and-risk-of-leukemia-and-brain-tumors-by-cancer-susceptibility-syndromes
#19
Johanna M Meulepas, Cécile M Ronckers, Johannes Merks, Michel E Weijerman, Jay H Lubin, Michael Hauptmann
Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk. Since empirical evidence is lacking in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about patterns of CT scans among CSS patients...
November 28, 2016: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
https://www.readbyqxmd.com/read/27878779/total-estimated-effective-doses-from-radiologic-imaging-modalities-of-children-with-cancer-a-single-center-experience
#20
Derya Özyörük, Suna Emir, Hacı Ahmet Demir, Gülşah Bayram Kabaçam, Bahattin Tunç
BACKGROUND: Recently, awareness of the cumulative radiation exposure for pediatric oncology patients has been increasing, together with increased survival rates and longer life expectancy. The aim of our study was to quantify the amount of ionising radiation from imaging modalities of pediatric oncology patients. METHODS: Eighty-eight patients who were diagnosed with childhood cancer and followed up for 5 years between 2004-2014 in our center were included in the study...
November 23, 2016: World Journal of Pediatrics: WJP
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