المؤلفون: Carrot-Zhang, Jian, Yao, Xiaotong, Devarakonda, Siddhartha, Deshpande, Aditya, Damrauer, Jeffrey S, Silva, Tiago Chedraoui, Wong, Christopher K, Choi, Hyo Young, Felau, Ina, Robertson, A Gordon, Castro, Mauro AA, Bao, Lisui, Rheinbay, Esther, Liu, Eric Minwei, Trieu, Tuan, Haan, David, Yau, Christina, Hinoue, Toshinori, Liu, Yuexin, Shapira, Ofer, Kumar, Kiran, Mungall, Karen L, Zhang, Hailei, Lee, Jake June-Koo, Berger, Ashton, Gao, Galen F, Zhitomirsky, Binyamin, Liang, Wen-Wei, Zhou, Meng, Moorthi, Sitapriya, Berger, Alice H, Collisson, Eric A, Zody, Michael C, Ding, Li, Cherniack, Andrew D, Getz, Gad, Elemento, Olivier, Benz, Christopher C, Stuart, Josh, Zenklusen, JC, Beroukhim, Rameen, Chang, Jason C, Campbell, Joshua D, Hayes, D Neil, Yang, Lixing, Laird, Peter W, Weinstein, John N, Kwiatkowski, David J, Tsao, Ming S, Travis, William D, Khurana, Ekta, Berman, Benjamin P, Hoadley, Katherine A, Robine, Nicolas, TCGA Research Network, Meyerson, Matthew, Govindan, Ramaswamy, Imielinski, Marcin

المصدر: Cell reports. 34(5)

مصطلحات موضوعية: TCGA Research Network, TCGA, driver, genome analysis, lung adenocarcinoma, noncoding, oncogene, precision oncology, structural variation, tumor suppressor, whole genome sequencing, Biochemistry and Cell Biology, Medical Physiology

الوصف: RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4q695702Test

المؤلفون: Giovanna Giordano, Elena Ferioli, Debora Guareschi, Alessandro Tafuni

المصدر: Cancers, Vol 15, Iss 21, p 5155 (2023)

مصطلحات موضوعية: endometrial dedifferentiated/undifferentiated carcinoma, the Cancer Genome Atlas (TCGA) Research Network, mismatch repair (MMR) gene mutations, DNA Polymerase Epsilon (POLE), Switch/Sucrose Non-Fermentable (SWI/SNF) complex, Tp53 mutations, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/15/21/5155Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/ff9b2ee08aef42b1ae548dbb7f0715e7Test

المؤلفون: Hmeljak, Julija, Sanchez-Vega, Francisco, Hoadley, Katherine A, Shih, Juliann, Stewart, Chip, Heiman, David, Tarpey, Patrick, Danilova, Ludmila, Drill, Esther, Gibb, Ewan A, Bowlby, Reanne, Kanchi, Rupa, Osmanbeyoglu, Hatice U, Sekido, Yoshitaka, Takeshita, Jumpei, Newton, Yulia, Graim, Kiley, Gupta, Manaswi, Gay, Carl M, Diao, Lixia, Gibbs, David L, Thorsson, Vesteinn, Iype, Lisa, Kantheti, Havish, Severson, David T, Ravegnini, Gloria, Desmeules, Patrice, Jungbluth, Achim A, Travis, William D, Dacic, Sanja, Chirieac, Lucian R, Galateau-Sallé, Françoise, Fujimoto, Junya, Husain, Aliya N, Silveira, Henrique C, Rusch, Valerie W, Rintoul, Robert C, Pass, Harvey, Kindler, Hedy, Zauderer, Marjorie G, Kwiatkowski, David J, Bueno, Raphael, Tsao, Anne S, Creaney, Jenette, Lichtenberg, Tara, Leraas, Kristen, Bowen, Jay, Felau, Ina, Zenklusen, Jean Claude, Akbani, Rehan, Cherniack, Andrew D, Byers, Lauren A, Noble, Michael S, Fletcher, Jonathan A, Robertson, A Gordon, Shen, Ronglai, Aburatani, Hiroyuki, Robinson, Bruce W, Campbell, Peter, Ladanyi, Marc, Ally, Adrian, Anur, Pavana, Armenia, Joshua, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Becich, Michael, Behrens, Carmen, Beroukhim, Rameen, Bielski, Craig, Bodenheimer, Tom, Bootwalla, Moiz S, Brooks, Denise, Byers, Lauren Averett, Cárcano, Flávio M, Carlsen, Rebecca, Carvalho, Andre L, Cheung, Dorothy, Chirieac, Lucian, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cope, Leslie, Crain, Daniel, Curley, Erin, Rienzo, Assunta De, DeFreitas, Timothy, Demchok, John A, Dhalla, Noreen

المصدر: Cancer Discovery. 8(12)

مصطلحات موضوعية: Rare Diseases, Lung Cancer, Biotechnology, Lung, Cancer, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Aged, Biomarkers, Tumor, Female, Histone-Lysine N-Methyltransferase, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Male, Mesothelioma, Middle Aged, Mutation, Pleural Neoplasms, Prognosis, Protein Methyltransferases, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, TCGA Research Network, Oncology and Carcinogenesis

الوصف: Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0515m295Test

المؤلفون: Robertson, A Gordon, Kim, Jaegil, Al-Ahmadie, Hikmat, Bellmunt, Joaquim, Guo, Guangwu, Cherniack, Andrew D, Hinoue, Toshinori, Laird, Peter W, Hoadley, Katherine A, Akbani, Rehan, Castro, Mauro AA, Gibb, Ewan A, Kanchi, Rupa S, Gordenin, Dmitry A, Shukla, Sachet A, Sanchez-Vega, Francisco, Hansel, Donna E, Czerniak, Bogdan A, Reuter, Victor E, Su, Xiaoping, Carvalho, Benilton de Sa, Chagas, Vinicius S, Mungall, Karen L, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Lu, Yiling, Klimczak, Leszek J, Zhang, Jiexin, Choo, Caleb, Ojesina, Akinyemi I, Bullman, Susan, Leraas, Kristen M, Lichtenberg, Tara M, Wu, Catherine J, Schultz, Nicholaus, Getz, Gad, Meyerson, Matthew, Mills, Gordon B, McConkey, David J, Network, TCGA Research, Albert, Monique, Alexopoulou, Iakovina, Ally, Adrian, Antic, Tatjana, Aron, Manju, Balasundaram, Miruna, Bartlett, John, Baylin, Stephen B, Beaver, Allison, Birol, Inanc, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bowlby, Reanne, Brooks, Denise, Broom, Bradley M, Bshara, Wiam, Burks, Eric, Cárcano, Flavio M, Carlsen, Rebecca, Carvalho, Benilton S, Carvalho, Andre L, Castle, Eric P, Castro, Patricia, Catto, James W, Chesla, David W, Chuah, Eric, Chudamani, Sudha, Cortessis, Victoria K, Cottingham, Sandra L, Crain, Daniel, Curley, Erin, Daneshmand, Siamak, Demchok, John A, Dhalla, Noreen, Djaladat, Hooman, Eckman, John, Egea, Sophie C, Engel, Jay, Felau, Ina, Ferguson, Martin L, Gardner, Johanna, Gastier-Foster, Julie M, Gerken, Mark, Gomez-Fernandez, Carmen R, Harr, Jodi

المصدر: Cell. 171(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Cancer Genomics, Urologic Diseases, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Aged, Cluster Analysis, DNA Methylation, Humans, MicroRNAs, Middle Aged, Muscle, Smooth, RNA, Long Noncoding, Survival Analysis, Urinary Bladder, Urinary Bladder Neoplasms, TCGA Research Network, APOBEC mutation, DNA methylation, basal mRNA subtype, lncRNA transcriptome, luminal mRNA subtype, microRNA, muscle-invasive bladder cancer, neoantigen, neuronal subtype, regulon, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9zq1g0w0Test
https://escholarship.org/content/qt9zq1g0w0/qt9zq1g0w0.pdfTest

المؤلفون: Robertson, A Gordon, Shih, Juliann, Yau, Christina, Gibb, Ewan A, Oba, Junna, Mungall, Karen L, Hess, Julian M, Uzunangelov, Vladislav, Walter, Vonn, Danilova, Ludmila, Lichtenberg, Tara M, Kucherlapati, Melanie, Kimes, Patrick K, Tang, Ming, Penson, Alexander, Babur, Ozgun, Akbani, Rehan, Bristow, Christopher A, Hoadley, Katherine A, Iype, Lisa, Chang, Matthew T, Network, TCGA Research, Abdel-Rahman, Mohamed H, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Benz, Christopher, Beroukhim, Rameen, Birol, Inanc, Bodenheimer, Tom, Bowen, Jay, Bowlby, Reanne, Brooks, Denise, Carlsen, Rebecca, Cebulla, Colleen M, Cherniack, Andrew D, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cibulskis, Kristian, Cope, Leslie, Coupland, Sarah E, Defreitas, Timothy, Demchok, John A, Desjardins, Laurence, Dhalla, Noreen, Esmaeli, Bita, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Gabriel, Stacey B, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Gershenwald, Jeffrey E, Getz, Gad, Griewank, Klaus G, Grimm, Elizabeth A, Hayes, D Neil, Hegde, Apurva M, Heiman, David I, Helsel, Carmen, Hobensack, Shital, Holt, Robert A, Hoyle, Alan P, Hu, Xin, Hutter, Carolyn M, Jager, Martine J, Jefferys, Stuart R, Jones, Corbin D, Jones, Steven JM, Kandoth, Cyriac, Kasaian, Katayoon, Kim, Jaegil, Kucherlapati, Raju, Lander, Eric, Lawrence, Michael S, Lazar, Alexander J, Lee, Semin, Leraas, Kristen M, Lin, Pei, Liu, Jia, Liu, Wenbin, Lolla, Laxmi, Lu, Yiling

المصدر: Cancer Cell. 32(2)

مصطلحات موضوعية: Eye Disease and Disorders of Vision, Cancer, Human Genome, Rare Diseases, Genetics, Biomarkers, Tumor, DNA Copy Number Variations, DNA Methylation, Eukaryotic Initiation Factor-1, Gene Expression Regulation, Neoplastic, Humans, Melanoma, Monosomy, Mutation, Phosphoproteins, Prognosis, RNA Splicing Factors, Serine-Arginine Splicing Factors, Tumor Suppressor Proteins, Ubiquitin Thiolesterase, Uveal Neoplasms, TCGA Research Network, EIF1AX, GNA11, GNAQ, SF3B1, SRSF2, TCGA, molecular subtypes, monosomy 3, noncoding RNA, uveal melanoma, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8nh9g2f7Test

المؤلفون: Ceccarelli, Michele, Barthel, Floris P, Malta, Tathiane M, Sabedot, Thais S, Salama, Sofie R, Murray, Bradley A, Morozova, Olena, Newton, Yulia, Radenbaugh, Amie, Pagnotta, Stefano M, Anjum, Samreen, Wang, Jiguang, Manyam, Ganiraju, Zoppoli, Pietro, Ling, Shiyun, Rao, Arjun A, Grifford, Mia, Cherniack, Andrew D, Zhang, Hailei, Poisson, Laila, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Rao, Arvind, Mikkelsen, Tom, Lau, Ching C, Yung, WK Alfred, Rabadan, Raul, Huse, Jason, Brat, Daniel J, Lehman, Norman L, Barnholtz-Sloan, Jill S, Zheng, Siyuan, Hess, Kenneth, Rao, Ganesh, Meyerson, Matthew, Beroukhim, Rameen, Cooper, Lee, Akbani, Rehan, Wrensch, Margaret, Haussler, David, Aldape, Kenneth D, Laird, Peter W, Gutmann, David H, Network, TCGA Research, Arachchi, Harindra, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barnett, Gene, Baylin, Stephen, Bell, Sue, Benz, Christopher, Bir, Natalie, Black, Keith L, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bristow, Christopher A, Butterfield, Yaron SN, Chen, Qing-Rong, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Coetzee, Simon G, Cohen, Mark L, Colman, Howard, Couce, Marta, D’Angelo, Fulvio, Davidsen, Tanja, Davis, Amy, Demchok, John A, Devine, Karen, Ding, Li, Duell, Rebecca, Elder, J Bradley, Eschbacher, Jennifer M, Fehrenbach, Ashley, Ferguson, Martin, Frazer, Scott, Fuller, Gregory, Fulop, Jordonna, Gabriel, Stacey B, Garofano, Luciano, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Giannini, Caterina, Gibson, William J, Hadjipanayis, Angela, Hayes, D Neil, Heiman, David I, Hermes, Beth, Hilty, Joe, Hoadley, Katherine A, Hoyle, Alan P, Huang, Mei

المصدر: Cell. 164(3)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Orphan Drug, Brain Cancer, Brain Disorders, Biotechnology, Human Genome, Rare Diseases, Neurosciences, Cancer, Adult, Brain Neoplasms, Cell Proliferation, Cluster Analysis, DNA Helicases, DNA Methylation, Epigenesis, Genetic, Glioma, Humans, Isocitrate Dehydrogenase, Middle Aged, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Signal Transduction, Telomerase, Telomere, Transcriptome, X-linked Nuclear Protein, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/507568tmTest

المؤلفون: Ciriello, Giovanni, Gatza, Michael L, Beck, Andrew H, Wilkerson, Matthew D, Rhie, Suhn K, Pastore, Alessandro, Zhang, Hailei, McLellan, Michael, Yau, Christina, Kandoth, Cyriac, Bowlby, Reanne, Shen, Hui, Hayat, Sikander, Fieldhouse, Robert, Lester, Susan C, Tse, Gary MK, Factor, Rachel E, Collins, Laura C, Allison, Kimberly H, Chen, Yunn-Yi, Jensen, Kristin, Johnson, Nicole B, Oesterreich, Steffi, Mills, Gordon B, Cherniack, Andrew D, Robertson, Gordon, Benz, Christopher, Sander, Chris, Laird, Peter W, Hoadley, Katherine A, King, Tari A, Perou, Charles M, Akbani, Rehan, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barr, Thomas, Beck, Andrew, Benz, Stephen, Berrios, Mario, Beroukhim, Rameen, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Brooks, Denise, Chin, Lynda, Cho, Juok, Chudamani, Sudha, Davidsen, Tanja, Demchok, John A, Dennison, Jennifer B, Ding, Li, Felau, Ina, Ferguson, Martin L, Frazer, Scott, Gabriel, Stacey B, Gao, JianJiong, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Gibson, William J, Hayes, D Neil, Heiman, David I, Holbrook, Andrea, Holt, Robert A, Hoyle, Alan P, Hu, Hai, Huang, Mei, Hutter, Carolyn M, Hwang, E Shelley, Jefferys, Stuart R, Jones, Steven JM, Ju, Zhenlin, Kim, Jaegil, Lai, Phillip H, Lawrence, Michael S, Leraas, Kristen M, Lichtenberg, Tara M, Lin, Pei, Ling, Shiyun, Liu, Jia, Liu, Wenbin, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T, Mardis, Elaine, Marks, Jeffrey, Marra, Marco A, McAllister, Cynthia

المصدر: Cell. 163(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Clinical Research, Genetics, Clinical Trials and Supportive Activities, Cancer, Antigens, CD, Breast Neoplasms, Cadherins, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Female, Hepatocyte Nuclear Factor 3-alpha, Humans, Models, Molecular, Mutation, Oligonucleotide Array Sequence Analysis, Oncogene Protein v-akt, Transcriptome, TCGA Research Network, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4tp5z1nrTest

المؤلفون: Brennan, Cameron W, Verhaak, Roel GW, McKenna, Aaron, Campos, Benito, Noushmehr, Houtan, Salama, Sofie R, Zheng, Siyuan, Chakravarty, Debyani, Sanborn, J Zachary, Berman, Samuel H, Beroukhim, Rameen, Bernard, Brady, Wu, Chang-Jiun, Genovese, Giannicola, Shmulevich, Ilya, Barnholtz-Sloan, Jill, Zou, Lihua, Vegesna, Rahulsimham, Shukla, Sachet A, Ciriello, Giovanni, Yung, WK, Zhang, Wei, Sougnez, Carrie, Mikkelsen, Tom, Aldape, Kenneth, Bigner, Darell D, Van Meir, Erwin G, Prados, Michael, Sloan, Andrew, Black, Keith L, Eschbacher, Jennifer, Finocchiaro, Gaetano, Friedman, William, Andrews, David W, Guha, Abhijit, Iacocca, Mary, O’Neill, Brian P, Foltz, Greg, Myers, Jerome, Weisenberger, Daniel J, Penny, Robert, Kucherlapati, Raju, Perou, Charles M, Hayes, D Neil, Gibbs, Richard, Marra, Marco, Mills, Gordon B, Lander, Eric, Spellman, Paul, Wilson, Richard, Sander, Chris, Weinstein, John, Meyerson, Matthew, Gabriel, Stacey, Laird, Peter W, Haussler, David, Getz, Gad, Chin, Lynda, Network, TCGA Research, Benz, Christopher, Barrett, Wendi, Ostrom, Quinn, Wolinsky, Yingli, Bose, Bikash, Boulos, Paul T, Boulos, Madgy, Brown, Jenn, Czerinski, Christine, Eppley, Matthew, Kempista, Thelma, Kitko, Teresa, Koyfman, Yakov, Rabeno, Brenda, Rastogi, Pawan, Sugarman, Michael, Swanson, Patricia, Yalamanchii, Kennedy, Otey, Ilana P, Liu, Yingchun Spring, Xiao, Yonghong, Auman, J Todd, Chen, Peng-Chieh, Hadjipanayis, Angela, Lee, Eunjung, Lee, Semin, Park, Peter J, Seidman, Jonathan, Yang, Lixing, Kalkanis, Steven, Poisson, Laila M, Raghunathan, Aditya, Scarpace, Lisa, Bressler, Ryan, Eakin, Andrea

المصدر: Cell. 155(2)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Brain Disorders, Biotechnology, Rare Diseases, Human Genome, Orphan Drug, Brain Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Brain Neoplasms, Female, Gene Expression Profiling, Gene Regulatory Networks, Glioblastoma, Humans, Male, Mutation, Proteome, Signal Transduction, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5vg1c1hsTest

المؤلفون: A. Gordon Robertson, Juliann Shih, Christina Yau, Ewan A. Gibb, Junna Oba, Karen L. Mungall, Julian M. Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M. Lichtenberg, Melanie Kucherlapati, Patrick K. Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A. Bristow, Katherine A. Hoadley, Lisa Iype, Matthew T. Chang, Andrew D. Cherniack, Christopher Benz, Gordon B. Mills, Roel G.W. Verhaak, Klaus G. Griewank, Ina Felau, Jean C. Zenklusen, Jeffrey E. Gershenwald, Lynn Schoenfield, Alexander J. Lazar, Mohamed H. Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M. Cebulla, Michelle D. Williams, Martine J. Jager, Sarah E. Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E. Woodman, Adrian Ally, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Rameen Beroukhim, Inanc Birol, Tom Bodenheimer, Jay Bowen, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Kristian Cibulskis, Leslie Cope, Timothy Defreitas, John A. Demchok, Laurence Desjardins, Noreen Dhalla, Martin L. Ferguson, Scott Frazer, Stacey B. Gabriel, Julie M. Gastier-Foster, Nils Gehlenborg, Mark Gerken, Gad Getz, Elizabeth A. Grimm, D. Neil Hayes, Apurva M. Hegde, David I. Heiman, Carmen Helsel, Shital Hobensack, Robert A. Holt, Alan P. Hoyle, Xin Hu, Carolyn M. Hutter, Stuart R. Jefferys, Corbin D. Jones, Steven J.M. Jones, Katayoon Kasaian, Jaegil Kim, Raju Kucherlapati, Eric Lander, Michael S. Lawrence, Semin Lee, Kristen M. Leraas, Pei Lin, Jia Liu, Wenbin Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Harshad S. Mahadeshwar, Odette Mariani, Marco A. Marra, Michael Mayo, Sam Meier, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Richard A. Moore, Lisle E. Mose, Andrew J. Mungall, Bradley A. Murray, Rashi Naresh, Michael S. Noble, Angeliki Pantazi, Michael Parfenov, Peter J. Park, Joel S. Parker, Charles M. Perou, Todd Pihl, Robert Pilarski, Alexei Protopopov, Amie Radenbaugh, Karan Rai, Nilsa C. Ramirez, Xiaojia Ren, Sheila M. Reynolds, Jeffrey Roach, Jason Roszik, Sara Sadeghi, Gordon Saksena, Xavier Sastre, Dirk Schadendorf, Jacqueline E. Schein, Steven E. Schumacher, Jonathan Seidman, Sahil Seth, Geetika Sethi, Margi Sheth, Yan Shi, Carol Shields, Ilya Shmulevich, Janae V. Simons, Arun D. Singh, Payal Sipahimalani, Tara Skelly, Heidi Sofia, Matthew G. Soloway, Xingzhi Song, Joshua Stuart, Qiang Sun, Huandong Sun, Angela Tam, Donghui Tan, Jiabin Tang, Roy Tarnuzzer, Barry S. Taylor, Nina Thiessen, Vesteinn Thorsson, Kane Tse, Umadevi Veluvolu, Doug Voet, Yunhu Wan, Zhining Wang, John N. Weinstein, Matthew D. Wilkerson, Lisa Wise, Tina Wong, Ye Wu, Liming Yang, Lixing Yang, Jiashan Zhang, Hailei Zhang, Erik Zmuda

المصدر: Cancer cell, vol 32, iss 2
Cancer Cell
Cancer Cell, 32(2), 204

مصطلحات موضوعية: 0301 basic medicine, Uveal Neoplasms, Cancer Research, Medizin, Eukaryotic Initiation Factor-1, Uveal Neoplasm, medicine.disease_cause, 0302 clinical medicine, Monosomy, Medicine, Melanoma, Cancer, Genetics, BAP1, Mutation, molecular subtypes, Tumor, Serine-Arginine Splicing Factors, SF3B1, Prognosis, Gene Expression Regulation, Neoplastic, SRSF2, Oncology, 030220 oncology & carcinogenesis, EIF1AX, DNA methylation, RNA Splicing Factors, uveal melanoma, Ubiquitin Thiolesterase, DNA Copy Number Variations, Oncology and Carcinogenesis, TCGA Research Network, monosomy 3, GNA11, Biology, noncoding RNA, Article, 03 medical and health sciences, Rare Diseases, GNAQ, Biomarkers, Tumor, Humans, Oncology & Carcinogenesis, Eye Disease and Disorders of Vision, Neoplastic, business.industry, Tumor Suppressor Proteins, Human Genome, Neurosciences, Cell Biology, DNA Methylation, TCGA, medicine.disease, Phosphoproteins, 030104 developmental biology, Gene Expression Regulation, Cancer research, business, Biomarkers

الوصف: Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, EIF1AX- and SRSF2/SF3B1-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate-risk clinical mutation subtypes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2b2bccbcc49408260b17e33b1915b29Test
https://hdl.handle.net/1887/115733Test

المؤلفون: Tirapelli, Daniel Pretti da Cunha, Cooper, Lee, Ling, Shiyun, Verhaak, Roel G.W., Zhang, Hailei, Wrensch, Margaret, Radenbaugh, Amie, Yung, W.K. Alfred, Grifford, Mia, Mikkelsen, Tom, Meyerson, Matthew, Huse, Jason, TCGA Research Network, Zoppoli, Pietro, Lau, Ching C., Barnholtz-Sloan, Jill S., Laird, Peter W., Akbani, Rehan, Anjum, Samreen, Noushmehr, Houtan, Zheng, Siyuan, Iavarone, Antonio, Malta, Tathiane, Rao, Ganesh, Rao, Aravind, Sabedot, Thais, Newton, Yulia, Carolotti, Jr., Carlos Gilberto, Rao, Arjun A., Pagnotta, Stefano, Gutmann, David, Manyam, Ganiraju, Poisson, Laila, Aldape, Kenneth, Rabadan, Raul, Murray, Bradley, Salama, Sofie, Barthel, Floris P., Haussler, David, Hess, Kenneth, Ceccarelli, Michele, Lehrman, Norman L., Cherniack, Andrew D., Morozova, Olena, Beroukhim, Rameen, Brat, Daniel J., Wang, Jiguang

المصدر: Cell, vol 164, iss 3

مصطلحات موضوعية: Adult, X-linked Nuclear Protein, TCGA Research Network, Medical and Health Sciences, Promoter Regions, Rare Diseases, Genetic, Genetics, Humans, Cluster Analysis, Telomerase, Cell Proliferation, Cancer, Brain Neoplasms, Human Genome, DNA Helicases, Neurosciences, Nuclear Proteins, Glioma, Telomere, DNA Methylation, Middle Aged, Biological Sciences, Isocitrate Dehydrogenase, Brain Disorders, Brain Cancer, Orphan Drug, Mutation, Transcriptome, Signal Transduction, Epigenesis, Biotechnology, Developmental Biology

الوصف: Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::849cb071a489e7f85f6d0bf1399527beTest
https://escholarship.org/uc/item/507568tmTest