المؤلفون: Suwala, Abigail K, Stichel, Damian, Schrimpf, Daniel, Maas, Sybren LN, Sill, Martin, Dohmen, Hildegard, Banan, Rouzbeh, Reinhardt, Annekathrin, Sievers, Philipp, Hinz, Felix, Blattner-Johnson, Mirjam, Hartmann, Christian, Schweizer, Leonille, Boldt, Henning B, Kristensen, Bjarne Winther, Schittenhelm, Jens, Wood, Matthew D, Chotard, Guillaume, Bjergvig, Rolf, Das, Anirban, Tabori, Uri, Hasselblatt, Martin, Korshunov, Andrey, Abdullaev, Zied, Quezado, Martha, Aldape, Kenneth, Harter, Patrick N, Snuderl, Matija, Hench, Jürgen, Frank, Stephan, Acker, Till, Brandner, Sebastian, Winkler, Frank, Wesseling, Pieter, Pfister, Stefan M, Reuss, David E, Wick, Wolfgang, von Deimling, Andreas, Jones, David TW, Sahm, Felix

المصدر: Acta Neuropathologica. 142(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Human Genome, Brain Cancer, Neurosciences, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Brain Neoplasms, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 7, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, DNA Methylation, Female, Gene Deletion, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Male, Middle Aged, Neuroectodermal Tumors, Primitive, PTEN Phosphohydrolase, Retinoblastoma Binding Proteins, Tumor Suppressor Protein p53, Ubiquitin-Protein Ligases, GBM, PNET, DNA methylation, Phenotype, Classification, Plasticity, Neurology & Neurosurgery

الوصف: Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.

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الوصول الحر: https://escholarship.org/uc/item/2kz927r8Test

المؤلفون: Arita, Hideyuki, Matsushita, Yuko, Machida, Ryunosuke, Yamasaki, Kai, Hata, Nobuhiro, Ohno, Makoto, Yamaguchi, Shigeru, Sasayama, Takashi, Tanaka, Shota, Higuchi, Fumi, Iuchi, Toshihiko, Saito, Kuniaki, Kanamori, Masayuki, Matsuda, Ken-Ichiro, Miyake, Yohei, Tamura, Kaoru, Tamai, Sho, Nakamura, Taishi, Uda, Takehiro, Okita, Yoshiko, Fukai, Junya, Sakamoto, Daisuke, Hattori, Yasuhiko, Pareira, Eriel, Hatae, Ryusuke, Ishi, Yukitomo, Miyakita, Yasuji, Tanaka, Kazuhiro, Takayanagi, Shunsaku, Otani, Ryohei, Sakaida, Tsukasa, Kobayashi, Keiichi, Saito, Ryuta, Kurozumi, Kazuhiko, Shofuda, Tomoko, Nonaka, Masahiro, Suzuki, Hiroyoshi, Shibuya, Makoto, Komori, Takashi, Sasaki, Hikaru, Mizoguchi, Masahiro, Kishima, Haruhiko, Nakada, Mitsutoshi, Sonoda, Yukihiko, Tominaga, Teiji, Nagane, Motoo, Nishikawa, Ryo, Kanemura, Yonehiro, Kuchiba, Aya, Narita, Yoshitaka, Ichimura, Koichi

المصدر: Acta Neuropathologica Communications. 8(1)

مصطلحات موضوعية: 1p/19q codeletion, CDKN2A, Glioma, IDH1/2, TERT, Adolescent, Adult, Aged, Aged, 80 and over, Astrocytoma, Brain Neoplasms, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Female, Glioblastoma, Glioma, Humans, Isocitrate Dehydrogenase, Karnofsky Performance Status, Male, Middle Aged, Multivariate Analysis, Mutation, Neoplasm Grading, Neurosurgical Procedures, Oligodendroglioma, Prognosis, Promoter Regions, Genetic, Proportional Hazards Models, Radiotherapy, Adjuvant, Retrospective Studies, Survival Rate, Telomerase, Young Adult

الوصف: TERT promoter mutations are commonly associated with 1p/19q codeletion in IDH-mutated gliomas. However, whether these mutations have an impact on patient survival independent of 1p/19q codeletion is unknown. In this study, we investigated the impact of TERT promoter mutations on survival in IDH-mutated glioma cases. Detailed clinical information and molecular status data were collected for a cohort of 560 adult patients with IDH-mutated gliomas. Among these patients, 279 had both TERT promoter mutation and 1p/19q codeletion, while 30 had either TERT promoter mutation (n = 24) or 1p/19q codeletion (n = 6) alone. A univariable Cox proportional hazard analysis for survival using clinical and genetic factors indicated that a Karnofsky performance status score (KPS) of 90 or 100, WHO grade II or III, TERT promoter mutation, 1p/19q codeletion, radiation therapy, and extent of resection (90-100%) were associated with favorable prognosis (p

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الوصول الحر: https://escholarship.org/uc/item/6zx7r406Test

المؤلفون: Lee, Eunice Y, Mak, Angel CY, Hu, Donglei, Sajuthi, Satria, White, Marquitta J, Keys, Kevin L, Eckalbar, Walter, Bonser, Luke, Huntsman, Scott, Urbanek, Cydney, Eng, Celeste, Jain, Deepti, Abecasis, Gonçalo, Kang, Hyun M, Germer, Soren, Zody, Michael C, Nickerson, Deborah A, Erle, David, Ziv, Elad, Rodriguez-Santana, Jose, Seibold, Max A, Burchard, Esteban G

المصدر: American Journal of Respiratory and Critical Care Medicine. 202(7)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Genetics, Human Genome, Biotechnology, Pediatric, Asthma, Clinical Research, Lung, Respiratory, Adolescent, Black People, Bronchi, Case-Control Studies, Cell Line, Child, Chromatin Immunoprecipitation, Chromosome Mapping, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 5, Esophageal Mucosa, Female, Forced Expiratory Volume, Gene Expression, Humans, Indians, North American, Linkage Disequilibrium, Male, Membrane Proteins, Myocytes, Smooth Muscle, Nasal Mucosa, Polymorphism, Single Nucleotide, Puerto Rico, Quantitative Trait Loci, Sequence Analysis, RNA, White People, Whole Genome Sequencing, Young Adult, admixed, FEV1, RNA sequencing, inflammatory, TMEM9 airway epithelial cells, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences

الوصف: Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma.

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الوصول الحر: https://escholarship.org/uc/item/01w476xfTest

المؤلفون: Yao, Jingwen, Hagiwara, Akifumi, Raymond, Catalina, Shabani, Soroush, Pope, Whitney B, Salamon, Noriko, Lai, Albert, Ji, Matthew, Nghiemphu, Phioanh L, Liau, Linda M, Cloughesy, Timothy F, Ellingson, Benjamin M

المصدر: Scientific reports. 10(1)

مصطلحات موضوعية: Chromosomes, Human, Pair 1, Humans, Glioma, Brain Neoplasms, Chromosome Deletion, Amines, Dihydroxyphenylalanine, Isocitrate Dehydrogenase, Contrast Media, Positron-Emission Tomography, Magnetic Resonance Imaging, Phantoms, Imaging, Mutation, Hydrogen-Ion Concentration, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Magnetic Phenomena, Cancer, Brain Disorders, Brain Cancer, Rare Diseases, Clinical Research, Biomedical Imaging

الوصف: Co-deletion of 1p/19q is a hallmark of oligodendroglioma and predicts better survival. However, little is understood about its metabolic characteristics. In this study, we aimed to explore the extracellular acidity of WHO grade II and III gliomas associated with 1p/19q co-deletion. We included 76 glioma patients who received amine chemical exchange saturation transfer (CEST) imaging at 3 T. Magnetic transfer ratio asymmetry (MTRasym) at 3.0 ppm was used as the pH-sensitive CEST biomarker, with higher MTRasym indicating lower pH. To control for the confounder factors, T2 relaxometry and L-6-18F-fluoro-3,4-dihydroxyphenylalnine (18F-FDOPA) PET data were collected in a subset of patients. We found a significantly lower MTRasym in 1p/19q co-deleted gliomas (co-deleted, 1.17% ± 0.32%; non-co-deleted, 1.72% ± 0.41%, P = 1.13 × 10-7), while FDOPA (P = 0.92) and T2 (P = 0.61) were not significantly affected. Receiver operating characteristic analysis confirmed that MTRasym could discriminate co-deletion status with an area under the curve of 0.85. In analysis of covariance, 1p/19q co-deletion status was the only significant contributor to the variability in MTRasym when controlling for age and FDOPA (P = 2.91 × 10-3) or T2 (P = 8.03 × 10-6). In conclusion, 1p/19q co-deleted gliomas were less acidic, which may be related to better prognosis. Amine CEST-MRI may serve as a non-invasive biomarker for identifying 1p/19q co-deletion status.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6k96p6mwTest

المؤلفون: Tan, Xiaochao, Banerjee, Priyam, Pham, Edward A, Rutaganira, Florentine UN, Basu, Kaustabh, Bota-Rabassedas, Neus, Guo, Hou-Fu, Grzeskowiak, Caitlin L, Liu, Xin, Yu, Jiang, Shi, Lei, Peng, David H, Rodriguez, B Leticia, Zhang, Jiaqi, Zheng, Veronica, Duose, Dzifa Y, Solis, Luisa M, Mino, Barbara, Raso, Maria Gabriela, Behrens, Carmen, Wistuba, Ignacio I, Scott, Kenneth L, Smith, Mark, Nguyen, Khanh, Lam, Grace, Choong, Ingrid, Mazumdar, Abhijit, Hill, Jamal L, Gibbons, Don L, Brown, Powel H, Russell, William K, Shokat, Kevan, Creighton, Chad J, Glenn, Jeffrey S, Kurie, Jonathan M

المصدر: Science Translational Medicine. 12(527)

مصطلحات موضوعية: Lung Cancer, Cancer, Lung, Rare Diseases, Adenocarcinoma of Lung, Animals, Chromosomes, Human, Pair 1, Enzyme-Linked Immunosorbent Assay, Golgi Apparatus, Humans, In Vitro Techniques, Membrane Proteins, Mice, Phosphotransferases (Alcohol Group Acceptor), X-Ray Microtomography, Biological Sciences, Medical and Health Sciences

الوصف: Heightened secretion of protumorigenic effector proteins is a feature of malignant cells. Yet, the molecular underpinnings and therapeutic implications of this feature remain unclear. Here, we identify a chromosome 1q region that is frequently amplified in diverse cancer types and encodes multiple regulators of secretory vesicle biogenesis and trafficking, including the Golgi-dedicated enzyme phosphatidylinositol (PI)-4-kinase IIIβ (PI4KIIIβ). Molecular, biochemical, and cell biological studies show that PI4KIIIβ-derived PI-4-phosphate (PI4P) synthesis enhances secretion and accelerates lung adenocarcinoma progression by activating Golgi phosphoprotein 3 (GOLPH3)-dependent vesicular release from the Golgi. PI4KIIIβ-dependent secreted factors maintain 1q-amplified cancer cell survival and influence prometastatic processes in the tumor microenvironment. Disruption of this functional circuitry in 1q-amplified cancer cells with selective PI4KIIIβ antagonists induces apoptosis and suppresses tumor growth and metastasis. These results support a model in which chromosome 1q amplifications create a dependency on PI4KIIIβ-dependent secretion for cancer cell survival and tumor progression.

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الوصول الحر: https://escholarship.org/uc/item/8dr2t5fbTest

المؤلفون: Xian, Rena R, Xie, Yi, Haley, Lisa M, Yonescu, Raluca, Pallavajjala, Aparna, Pittaluga, Stefania, Jaffe, Elaine S, Duffield, Amy S, McCall, Chad M, Gheith, Shereen MF, Gocke, Christopher D

المصدر: Blood Cancer Journal. 10(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Human Genome, Rare Diseases, Genetics, Hematology, Clinical Research, Cancer, Biotechnology, Lymphoma, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, CREB-Binding Protein, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 16, Female, Humans, Lymphoma, Follicular, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, STAT6 Transcription Factor, Translocation, Genetic, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology, Oncology and carcinogenesis

الوصف: The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic review, FISH, SNP-microarray, and next-generation sequencing of 16 cases of dFL. We found unique morphologic features, including interstitial sclerosis, microfollicle formation, and rounded nuclear cytology, confirmed absence of t(14;18) and recurrent deletion of 1p36, and showed a novel association with deletion/CN-LOH of 16p13 (inclusive of CREBBP, CIITA, and SOCS1). Mutational profiling demonstrated near-uniform mutations in CREBBP and STAT6, with clonal dominance of CREBBP, among other mutations typical of germinal-center B-cell lymphomas. Frequent CREBBP and CIITA codeletion/mutation suggested a mechanism for immune evasion, while subclonal STAT6 activating mutations with concurrent SOCS1 loss suggested a mechanism of BCL-xL/BCL2L1 upregulation in the absence of BCL2 rearrangements. A review of the literature showed significant enrichment for 16p13 and 1p36 loss/CN-LOH, STAT6 mutation, and CREBBP and STAT6 comutation in dFL, as compared with conventional FL. With this comprehensive approach, our study demonstrates confirmatory and novel genetic associations that can aid in the diagnosis and subclassification of this rare type of lymphoma.

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الوصول الحر: https://escholarship.org/uc/item/39n9r2kjTest

المؤلفون: Barthel, Floris P, Johnson, Kevin C, Varn, Frederick S, Moskalik, Anzhela D, Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J, Abiola, Olajide, Aldape, Kenneth, Alfaro, Kristin D, Alpar, Donat, Amin, Samirkumar B, Ashley, David M, Bandopadhayay, Pratiti, Barnholtz-Sloan, Jill S, Beroukhim, Rameen, Bock, Christoph, Brastianos, Priscilla K, Brat, Daniel J, Brodbelt, Andrew R, Bruns, Alexander F, Bulsara, Ketan R, Chakrabarty, Aruna, Chakravarti, Arnab, Chuang, Jeffrey H, Claus, Elizabeth B, Cochran, Elizabeth J, Connelly, Jennifer, Costello, Joseph F, Finocchiaro, Gaetano, Fletcher, Michael N, French, Pim J, Gan, Hui K, Gilbert, Mark R, Gould, Peter V, Grimmer, Matthew R, Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D, Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde CM, LaViolette, Peter S, Li, Meihong, Lichter, Peter, Ligon, Keith L, Lowman, Allison K, Malta, Tathiane M, Mazor, Tali, McDonald, Kerrie L, Molinaro, Annette M, Nam, Do-Hyun, Nayyar, Naema, Ng, Ho Keung, Ngan, Chew Yee, Niclou, Simone P, Niers, Johanna M, Noushmehr, Houtan, Noorbakhsh, Javad, Ormond, D Ryan, Park, Chul-Kee, Poisson, Laila M, Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K, Schuster, Michael, Shaw, Brian L, Short, Susan C, Smitt, Peter A Sillevis, Sloan, Andrew E, Smits, Marion, Suzuki, Hiromichi, Tabatabai, Ghazaleh, Van Meir, Erwin G, Watts, Colin, Weller, Michael, Wesseling, Pieter, Westerman, Bart A, Widhalm, Georg, Woehrer, Adelheid, Yung, WK Alfred, Zadeh, Gelareh, Huse, Jason T, De Groot, John F, Stead, Lucy F, Verhaak, Roel GW

المصدر: Nature. 576(7785)

مصطلحات موضوعية: Neurosciences, Brain Disorders, Cancer, Rare Diseases, Brain Cancer, Genetics, Adult, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Disease Progression, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Polymorphism, Single Nucleotide, Recurrence, GLASS Consortium, General Science & Technology

الوصف: The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

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الوصول الحر: https://escholarship.org/uc/item/0km0h0p6Test

المؤلفون: Dix, David B, Fernandez, Conrad V, Chi, Yueh-Yun, Mullen, Elizabeth A, Geller, James I, Gratias, Eric J, Khanna, Geetika, Kalapurakal, John A, Perlman, Elizabeth J, Seibel, Nita L, Ehrlich, Peter F, Malogolowkin, Marcio, Anderson, James, Gastier-Foster, Julie, Shamberger, Robert C, Kim, Yeonil, Grundy, Paul E, Dome, Jeffrey S

المصدر: Journal of Clinical Oncology. 37(30)

مصطلحات موضوعية: Clinical Research, Cancer, Pediatric, Pediatric Cancer, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adolescent, Adult, Biomarkers, Tumor, Chromosomes, Human, Pair 1, Female, Humans, Kidney Neoplasms, Loss of Heterozygosity, Male, Progression-Free Survival, Prospective Studies, Retrospective Studies, Wilms Tumor, Young Adult, AREN0532 and AREN0533 study committees, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: PurposeIn National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.MethodsPatients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies.ResultsLOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease (P = .042), and 61.3% for patients with stage III/IV disease (P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%).ConclusionAugmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

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الوصول الحر: https://escholarship.org/uc/item/8kv0f31nTest

المؤلفون: Chen, Hui, Thomas, Cheddhi, Munoz, Felipe Andres, Alexandrescu, Sanda, Horbinski, Craig M, Olar, Adriana, McGuone, Declan, Camelo-Piragua, Sandra, Wang, Lu, Pentsova, Elena, Phillips, Joanna, Aldape, Kenneth, Chen, Wen, Iafrate, A John, Chi, Andrew S, Zagzag, David, Golfinos, John G, Placantonakis, Dimitris G, Rosenblum, Marc, Ohman-Strickland, Pamela, Hameed, Meera, Snuderl, Matija

المصدر: Neuro-Oncology. 21(9)

مصطلحات موضوعية: Cancer, Clinical Research, Adolescent, Adult, Aged, Aged, 80 and over, Aneuploidy, Brain Neoplasms, Chemotherapy, Adjuvant, Child, Chromosomal Instability, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Female, Humans, In Situ Hybridization, Fluorescence, Isocitrate Dehydrogenase, Male, Middle Aged, Neoadjuvant Therapy, Neurosurgical Procedures, Oligodendroglioma, Prognosis, Progression-Free Survival, Radiotherapy, Adjuvant, Survival Rate, Young Adult, 1p/19q codeletion, glioma, oligodendroglioma, polysomy, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: BackgroundChromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p/19q status.MethodsWe analyzed 412 histologic oligodendroglial tumors with use of 1p/19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p/19q was performed. Polysomy was defined as more than two 1q and 19p signals in cells. Tumors were divided into groups on the basis of their 1p/19q status and polysomy and were compared for progression-free survival (PFS) and overall survival (OS).ResultsIn our cohort, 333 tumors (81%) had 1p/19q loss; of these, 195 (59%) had concurrent polysomy and 138 (41%) lacked polysomy, 79 (19%) had 1p/19q maintenance; of these, 30 (38%) had concurrent polysomy and 49 (62%) lacked polysomy. In agreement with prior studies, the group with 1p/19q loss had significantly better PFS and OS than did the group with 1p/19q maintenance (P < 0.0001 each). Patients with 1p/19q loss and polysomy showed significantly shorter PFS survival than patients with 1p/19q codeletion only (P < 0.0001), but longer PFS and OS than patients with 1p/19q maintenance (P < 0.01 and P < 0.0001). There was no difference in survival between tumors with >30% polysomic cells and those with

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الوصول الحر: https://escholarship.org/uc/item/4sd2j0m5Test

المؤلفون: Carter, Lauren B, Battaglia, Agatino, Cherry, Athena, Manning, Melanie A, Ruzhnikov, Maura RZ, Bird, Lynne M, Dowsett, Leah, Graham, John M, Alkuraya, Fowzan S, Hashem, Mais, Dinulos, Mary Beth, Vallee, Stephanie, Adam, Margaret P, Glass, Ian, Beck, Anita E, Stevens, Cathy A, Zackai, Elaine, McDougall, Carey, Keena, Beth, Peron, Angela, Vignoli, Aglaia, Seaver, Laurie H, Slavin, Thomas P, Hudgins, Louanne

المصدر: American Journal of Medical Genetics Part A. 179(8)

مصطلحات موضوعية: Perinatal Period - Conditions Originating in Perinatal Period, Infant Mortality, Epilepsy, Neurosciences, Clinical Research, Pediatric, Brain Disorders, Neurodegenerative, Physical Injury - Accidents and Adverse Effects, Intellectual and Developmental Disabilities (IDD), Preterm, Low Birth Weight and Health of the Newborn, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Mental health, Neurological, Good Health and Well Being, Chromosome Deletion, Chromosome Disorders, Chromosomes, Human, Pair 1, Diagnosis, Differential, Female, Humans, Hypoxia-Ischemia, Brain, Infant, Newborn, Male, Phenotype, Pregnancy, Psychological Distress, 1p36, distress, hypoxic ischemic encephalopathy, Genetics, Clinical Sciences

الوصف: 1p36 deletion syndrome is a well-described condition with a recognizable phenotype, including cognitive impairment, seizures, and structural brain anomalies such as periventricular leukomalacia (PVL). In a large series of these individuals by Battaglia et al., "birth history was notable in 50% of the cases for varying degrees of perinatal distress." Given the potential for perinatal distress, seizures and PVL, we questioned if this disorder has clinical overlap with hypoxic ischemic encephalopathy (HIE). We reviewed the medical records of 69 individuals with 1p36 deletion to clarify the perinatal phenotype of this disorder and determine if there is evidence of perinatal distress and/or hypoxic injury. Our data provides evidence that these babies have signs of perinatal distress. The majority (59% term; 75% preterm) needed resuscitation and approximately 18% had cardiac arrest. Most had abnormal brain imaging (84% term; 73% preterm) with abnormal white matter findings in over half of patients. PVL or suggestion of "hypoxic insult" was present in 18% of term and 45% of preterm patients. In conclusion, individuals with 1p36 deletion have evidence of perinatal distress, white matter changes, and seizures, which can mimic HIE but are likely related to their underlying chromosome disorder.

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الوصول الحر: https://escholarship.org/uc/item/8dn5g2fqTest