The presence of two DNA alterations in RB1 is associated with poor overall survival independently of other clinicopathologic factors in metastatic castration-resistant prostate cancer. Cell 2018;174:758-69.e9. Cancer Cell. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer Cell, Vol. Cancer Inst. Ultimately, the apparent neutral prognosis of metastatic prostate cancer harbouring AKT1/PIK3CA mutations should be balanced against the fact that AKT1/PIK3CA mutations appear to be enriched in mCRPC compared with localised disease, ... Genomic hallmarks and structural variation in metastatic prostate cancer. Regarding aneuploidy, about 75% of locoregional prostate cancer genomes have chromosomal arm-level alterations, and 23% possessed ≥5 arm-level alterations ( 44 ). 2017. Sacramento, CA 95817. Abstract. 916-734-5959. While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. A proposed approach to accelerate evidence generation for genomic-based technologies in the context of a learning health system. 2017; 541: 359-364. 2018 10 18; 175(3):889. Quigley, D. A. et al. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. Cell. Nature. Cell 174 , 758–769.e9 (2018). Numerous mechanisms of resistance arise in response to treatment with second-generation androgen receptor (AR) pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). No. . However, resistance eventually develops, leading to a lethal phenotype known as metastatic … Abstract. Oncoimmunology. Cancer Cell. ). 1. et al. View on PubMed; Hagihara K, Chan S, Zhang L, Oh DY, Wei XX, Simko J, Fong L. Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, et al. Ten patients from the investigated cohorts with metastatic prostate cancer had multiple metastatic sites sequenced. Genomic Alteration During Metastasis of Lung Adenocarcinoma. Washington University School of Medicine’s 1,300 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. Cell 2018;174:758-69. Genomic hallmarks and structural variation in metastatic prostate cancer. Article CAS PubMed PubMed Central Google Scholar Pre-doctoral Fellowship, Department of Defense, Breast Cancer Research Program, 2010. Cell, 175 (2018), p. 889. Sponsor: NIH/NCI, Sponsor Award ID: R01CA240984 September 1, 2017 - August 31, 2022 - Targeted regulation of transcript stability through RNA methylation and intron retention, Principal Investigator. In addition, Wnt/β-catenin pathway activation and β-catenin mutations are associated with enzalutamide resistance and poor overall survival. 2017. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Integrative whole-genome and -transcriptome sequencing provides a comprehensive view of structural variations that affect major regulators in prostate cancer and would escape detection by exome-based approaches. 30033370: Cell Humoral immune response to alpha-methylacyl-CoA racemase and prostate cancer. Genomic hallmarks of localized, non-indolent prostate cancer. explore the genomic hallmarks and structural variation in metastatic PC, including bone metastatic CRPCs . 14: Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer A recent study in localized prostate cancer demonstrated clusters of genomic rearrangements each occurring in 5%–6% of samples (. 2016;30(4):563-577 47. Structural alterations driving castration-resistant prostate cancer revealed by linked-read genome … 18077443 While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. TCGA data are generated across a number of different cancer types. Locoregional prostate cancer cohorts have a highly variable structural variant burden, with a median of 19 structural variants per genome (range between 0 and 499, Table 2) . Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. 15173267: J. Natl. Full-Text. Cell. Benassi B, Flavin R, Marchionni L. et al. DOI PubMed; 15. Background. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, Foye A, Kothari V, Perry MD, Bailey AM, Playdle D, Barnard TJ, Zhang Androgens mediate the biological effects through the androgen receptor … Cell 2018 ;174(3):758–769.e9[Published correction appears in Cell 2018;175(3):889.]. Genomic hallmarks and structural variation in metastatic prostate cancer. Quigley et al. Cell. ... Quigley DA, Dang HX, Zhao SG, et al. 2020 07 15; 26(14):3517-3524. Bionano Saphyr Genome Imaging Instrument finds structural variations larger than 500 bp, unbiased and genome-wide, with the highest sensitivities and the lowest false positive rates, down to 1% variant allele fraction. Benassi B, Flavin R, Marchionni L. et al. Quigley, D. A. et al. View on PubMed; Horlbeck MA, Xu A, Wang M, Bennett NK, Park CY, Bogdanoff D, Adamson B, Chow ED, Kampmann M, Peterson TR, Nakamura K, Fischbach MA, Weissman JS, Gilbert LA. 1 –6 Genomic profiling of metastatic biopsies of mCRPC has revealed multiple molecular alterations, including alterations of DNA damage repair (DDR) … Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease, and the second leading cause of cancer-related mortality in men in the United States . Genomic hallmarks and structural variation in metastatic prostate cancer. 916-734-2222. 916-734-2222. However, these researches do not pay more attention on the state of tumor cells after metastatic colonization and also do not explore the differences between the tumor cells and normal cells in bone. A study of the repetitive structure and distribution of short motifs in human genomic … Antonarakis ES, Velho PI, Agarwal N, et al. Cell 2018;174:758-769.e9. View on PubMed; Hagihara K, Chan S, Zhang L, Oh DY, Wei XX, Simko J, Fong L. Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, Alumkal JJ, et al. 2018;175:889. Viswanathan SR, Ha G, Hoff AM, Wala JA, Carrot-Zhang J, Whelan CW, et al. Genomic hallmarks and structural variation in metastatic prostate cancer [published ... Montgomery B, Cheng HH, et al. Genomic hallmarks and structural variation in metastatic prostate cancer. 2279 45th Street. The relationship between sex steroid hormones (eg, androgen, estrogen, and progesterone), their cognate receptors, and genomic stability lie at the center of endocrine-driven cancer development, progression, and therapeutic resistance. Humoral response profiling reveals pathways to prostate cancer progression. In 1941, Huggins and Hodges [] demonstrated the clinical benefit of hormonal manipulation in patients with metastatic prostate cancer, establishing prostate cancer as an androgen-dependent disease.Since then, androgen deprivation therapy (ADT) has been the mainstay of prostate cancer treatment. Dardenne E, Beltran H, Benelli M. et al. Among these, point mutations in the ligand binding domain can transform antagonists into agonists, driving the disease through activation of AR signaling. Crossref , Medline , … CellJuly 19, 2018. No. Genomic hallmarks and structural variation in metastatic prostate cancer. 4501 X St. 2018; 175 : 889 View in Article Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Viswanathan SR, Ha G, Hoff AM, Wala JA, Carrot-Zhang J, Whelan CW, et al. 2019; 8(1):e1486953. Using genetic sequencing, scientists have revealed the complete DNA makeup of more than 100 aggressive prostate tumors, pinpointing important genetic … Quigley DA, Dang HX, Zhao SG. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer Cell. Primary prostate cancers are usually characterized by a diploid genome, low mutational burden, genomic rearrangements mainly involving the ETS genes and copy number aberrations, including deletions and amplifications. The overall genomic burden is associated with tumor grade [ 9 - 12] and with biochemical recurrence [ 13, 14]. 2017. Cell. Cell, 175 (2018), p. 889. The latter is particularly relevant for advanced prostate cancer, in which chromothripsis and structural variations are highly prevalent. Androgens mediate the biological effects through the androgen receptor … Like TMB, the structural variant burden correlates with Gleason score (17 in Gleason 6 disease compared to 22 in Gleason 7, p < 0.001) ( Table 2 ) ( 16 ). 2019; 8(1):e1486953. Nature. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Información del artículo Genomic hallmarks and structural variation in metastatic prostate cancer While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Abstract: While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Genomic hallmarks and structural variation in metastatic prostate cancer. Proposal for New e-Book Architecture combining a Bi-Lingual eTOCs, English & Spanish with NLPs results of Text Analysis: Series B, Genomics, Volume 1 & 2 and Series C, Cancer, Volume 1 & 2 Author: Aviva Lev-Ari, PhD, RN For the following FOUR VOLUMES: GENOMICS 1&2 and CANCER 1&2We will have NLP - 10-Step Workflow protocol… PURPOSE Comprehensive genomic profiling (CGP) is increasingly used for routine clinical management of prostate cancer. Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, et al. CAS PubMed Article PubMed Central Google Scholar 4. Apalutamide, brand named Erleada, significantly improved metastasis-free survival, a composite endpoint measuring the length of time before tumors metastasize to other parts of the body or until death occurs. [ PMC free article ] [ PubMed ] [ Google Scholar ] 2016;30(4):563-577 47. The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects have provided RNA-seq data from a large number of cancer and non-cancer samples, providing an exceptional resource for exploring gene expression in cancer research [56,57]. 2018 10 18; 175(3):889. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. 2018 07 26; 174(3):758-769.e9. Sacramento, CA 95817. CDK12-altered prostate cancer: Clinical features and therapeutic outcomes to standard systemic therapies, PARP … The median follow-up was 66.6 mo. 1 –6 Genomic profiling of metastatic biopsies of mCRPC has revealed multiple molecular alterations, including alterations of DNA damage repair (DDR) … Cell. View Article PubMed/NCBI Google Scholar 19. N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. 2018;174:758–769. Patients with CDK12 mutant prostate cancer exhibited shorter time to metastasis (median = 34.9 mo, p = 0.004) and development of castration-resistant disease (median = 32.7 mo, p < 0.001), compared with other genomic subtypes, with shorter time to PSA progression on first-line ARPI treatment of metastatic castration-resistant disease (median = 3.6 mo, p … Cell 174 , 758–769.e9 (2018). Unlike BRCA2, loss of ATM or CDK12 does not generate typical genomic … Metastatic castration-resistant prostate cancer (mCRPC) remains incurable, despite incremental improvements provided by multiple agents, including new-generation hormone therapies, taxane chemotherapy, and PARP inhibitors. Genomic hallmarks and structural variation in metastatic prostate cancer. Correction Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer DavidA. To inform targeted treatment strategies, 3,476 clinically advanced prostate tumors were analyzed by CGP for genomic alterations (GAs) and signatures of genomic instability. For two of the patients (A17 and A34), the primary prostate cancer and all of the metastatic sites showed signs of HRD and had higher than 0.9 HRDetect scores. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Quigley DA, et al. 2018; 174 ( 69.e9 ) : 758 View in Article Eukaryotic Sexual Reproduction Evoked "with a Little Help from My Friends". Cell. View on PubMed Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer Cell. 2018 Jul 26;174(3):758-769.e9.doi: 10.1016/j.cell.2018.06.039. Epub 2018 Jul 19. Authors Herein, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500× coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, … Background. Quigley DA, Dang HX, Zhao SG, et al: Genomic hallmarks and structural variation in metastatic prostate cancer [Erratum: Cell 175:889, 2018]. ... Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Genomic hallmarks and structural variation in metastatic prostate cancer. July 19, 2018. Poster Winner, UCSF Breast Oncology Retreat, 2014. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer David A. Quigley *1,2 , Ha X. Dang *3,4 , Shuang G. Zhao *5 , Paul Lloyd 6 , Rahul Aggarwal 6 , Joshi J. Alumkal 7,8 , Adam Foye 6 , Vishal Kothari 9 , Marc Perry 9 , Adina M. Bailey 6 , Denise Playdle 6 , Travis J. Barnard 9 , Cell. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X nor … While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. [15,16] How these collective, dynamic genetic changes can be assessed, curated, and translated into improved clinical intervention remains an … Genomic hallmarks and structural variation in metastatic prostate cancer. Cell. Integrative clinical genomics of metastatic cancer. T32 Fellow in Molecular and Cellular Mechanisms of Cancer, UCSF, Helen Diller Cancer Center, 2017. Cell. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X nor … Primary Phone: 800-362-5566. Mismatch repair deficiency in metastatic prostate cancer: Response to PD-1 blockade and standard therapies. 14: Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. 170:1059-1061. Quigley DA, Dang HX, Zhao SG, et al. . Clin Cancer Res. View on PubMed NGS was performed on patients’ metastatic prostate cancer biopsy samples, primary prostatectomy samples, or plasma cell-free DNA (cfDNA). Prostate cancer (PC) is a highly heterogeneous disease. Cell 174 , 758–769.e9 (2018). Quigley DA, Dang HX, Zhao SG, et al. METHODS Prostate cancer samples (1,660 primary site and 1,816 metastatic site tumors … In addition, previous studies have demonstrated that SVs may define subtypes of ovarian, pancreatic, and breast cancers (. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Quigley DA, Dang HX, Zhao SG, Lloyd P, Aggarwal R, et al. Invited Mini-Symposium Speaker - Cancer Cell Biology, American Society of Cell Biology Annual Meeting - SF, 2013. Cell 2018).Scripts employed during the analysis are available on github: 174, No. Introduction. Posadas EM, Chi KN, de Wit R, de Jonge MJA, Attard G, Friedlander TW, Yu MK, Hellemans P, Chien C, Abrams C, Jiao JJ, Saad F. Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. cell 174 , 758–769.e9 (2018). Cell 174: 758 - 769.e9 , 2018 Crossref , … Cell. Androgen receptor (AR) signaling is a hallmark of prostate cancer (PC). 2018;174(3):758-769 46. Mapping the Genetic Landscape of Human Cells. In advanced PC, BRCA2 is the most commonly aberrant gene; other reported defects involve ATM and CDK12 [1]. Purpose: The genomic underpinning of clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer is unclear. Moreover, androgen deprivation therapy (ADT) is highly effective in most patients with metastatic PC. Driving Directions. Dardenne E, Beltran H, Benelli M. et al. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. At MI, metastatic biopsies were analyzed ... Genomic hallmarks and structural variation in metastatic prostate cancer. ... structural variants at the genome-wide level are still poorly defined. Genomic hallmarks and structural variation in metastatic prostate cancer. Información del artículo Genomic hallmarks and structural variation in metastatic prostate cancer While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. 14. Our tools and platforms provide unparalleled structural variation detection for cancer research. 2017;548(7667):297-303 5. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. 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