241 results on '"Houlahan, Kathleen E"'
Search Results
2. A polygenic two-hit hypothesis for prostate cancer
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Houlahan, Kathleen E, Livingstone, Julie, Fox, Natalie S, Kurganovs, Natalie, Zhu, Helen, Sietsma Penington, Jocelyn, Jung, Chol-Hee, Yamaguchi, Takafumi N, Heisler, Lawrence E, Jovelin, Richard, Costello, Anthony J, Pope, Bernard J, Kishan, Amar U, Corcoran, Niall M, Bristow, Robert G, Waszak, Sebastian M, Weischenfeldt, Joachim, He, Housheng H, Hung, Rayjean J, Hovens, Christopher M, and Boutros, Paul C
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Genetics ,Aging ,Prostate Cancer ,Urologic Diseases ,Prevention ,Genetic Testing ,Human Genome ,Good Health and Well Being ,Male ,Humans ,Prostatic Neoplasms ,Risk Factors ,Prognosis ,Genetic Predisposition to Disease ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Prostate cancer is one of the most heritable cancers. Hundreds of germline polymorphisms have been linked to prostate cancer diagnosis and prognosis. Polygenic risk scores can predict genetic risk of a prostate cancer diagnosis. Although these scores inform the probability of developing a tumor, it remains unknown how germline risk influences the tumor molecular evolution. We cultivated a cohort of 1250 localized European-descent patients with germline and somatic DNA profiling. Men of European descent with higher genetic risk were diagnosed earlier and had less genomic instability and fewer driver genes mutated. Higher genetic risk was associated with better outcome. These data imply a polygenic "two-hit" model where germline risk reduces the number of somatic alterations required for tumorigenesis. These findings support further clinical studies of polygenic risk scores as inexpensive and minimally invasive adjuncts to standard risk stratification. Further studies are required to interrogate generalizability to more ancestrally and clinically diverse populations.
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- 2023
3. Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture.
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Yuan, Jiapei, Houlahan, Kathleen E, Ramanand, Susmita G, Lee, Sora, Baek, GuemHee, Yang, Yang, Chen, Yong, Strand, Douglas W, Zhang, Michael Q, Boutros, Paul C, and Mani, Ram S
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Cancer ,Aging ,Prostate Cancer ,Human Genome ,Urologic Diseases ,Genetics ,Biotechnology ,1.1 Normal biological development and functioning ,Aetiology ,2.1 Biological and endogenous factors ,Underpinning research ,Male ,Humans ,Alleles ,Genome-Wide Association Study ,Transcriptome ,Prostatic Neoplasms ,Genomics ,Mutation ,Germ Cells ,Polymorphism ,Single Nucleotide ,Oncology and Carcinogenesis - Abstract
Prostate cancer is one of the most heritable human cancers. Genome-wide association studies have identified at least 185 prostate cancer germline risk alleles, most noncoding. We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors. To supplement these 31, we verified transcriptional targets for 56 additional risk alleles using linear proximity and linkage disequilibrium analysis in localized prostate tumors. Some individual risk alleles influenced multiple target genes; others specifically influenced only distal genes while leaving proximal ones unaffected. Several risk alleles exhibited widespread germline-somatic interactions in transcriptional regulation, having different effects in tumors with loss of PTEN or RB1 relative to those without. These data clarify functional prostate cancer risk alleles in large linkage blocks and outline a strategy to model multidimensional transcriptional regulation.SignificanceMany prostate cancer germline risk alleles are enriched in the noncoding regions of the genome and are hypothesized to regulate transcription. We present a 3D genomics framework to unravel risk SNP function and describe the widespread germline-somatic interplay in transcription control. This article is highlighted in the In This Issue feature, p. 2711.
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- 2022
4. Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena
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Khoo, Amanda, Liu, Lydia Y, Sadun, Taylor Y, Salmasi, Amirali, Pooli, Aydin, Felker, Ely, Houlahan, Kathleen E, Ignatchenko, Vladimir, Raman, Steven S, Sisk, Anthony E, Reiter, Robert E, Boutros, Paul C, and Kislinger, Thomas
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Cancer ,Urologic Diseases ,Aging ,Humans ,Male ,Multiparametric Magnetic Resonance Imaging ,Neoplasm Grading ,Prostate ,Prostatic Neoplasms ,Proteomics ,Multiparametric magnetic resonance imaging ,Prostate cancer ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology ,Oncology and carcinogenesis - Abstract
Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors (i.e., International Society of Urological Pathology (ISUP) Grade Group 2)-twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.
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- 2022
5. Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH
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Hung, King L, Luebeck, Jens, Dehkordi, Siavash R, Colón, Caterina I, Li, Rui, Wong, Ivy Tsz-Lo, Coruh, Ceyda, Dharanipragada, Prashanthi, Lomeli, Shirley H, Weiser, Natasha E, Moriceau, Gatien, Zhang, Xiao, Bailey, Chris, Houlahan, Kathleen E, Yang, Wenting, González, Rocío Chamorro, Swanton, Charles, Curtis, Christina, Jamal-Hanjani, Mariam, Henssen, Anton G, Law, Julie A, Greenleaf, William J, Lo, Roger S, Mischel, Paul S, Bafna, Vineet, and Chang, Howard Y
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Biological Sciences ,Genetics ,Bioengineering ,Nanotechnology ,Cancer ,Biotechnology ,Human Genome ,Humans ,Oncogenes ,DNA ,Neoplasms ,Glioblastoma ,ErbB Receptors ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Extrachromosomal DNA (ecDNA) is a common mode of oncogene amplification but is challenging to analyze. Here, we adapt CRISPR-CATCH, in vitro CRISPR-Cas9 treatment and pulsed field gel electrophoresis of agarose-entrapped genomic DNA, previously developed for bacterial chromosome segments, to isolate megabase-sized human ecDNAs. We demonstrate strong enrichment of ecDNA molecules containing EGFR, FGFR2 and MYC from human cancer cells and NRAS ecDNA from human metastatic melanoma with acquired therapeutic resistance. Targeted enrichment of ecDNA versus chromosomal DNA enabled phasing of genetic variants, identified the presence of an EGFRvIII mutation exclusively on ecDNAs and supported an excision model of ecDNA genesis in a glioblastoma model. CRISPR-CATCH followed by nanopore sequencing enabled single-molecule ecDNA methylation profiling and revealed hypomethylation of the EGFR promoter on ecDNAs. We distinguished heterogeneous ecDNA species within the same sample by size and sequence with base-pair resolution and discovered functionally specialized ecDNAs that amplify select enhancers or oncogene-coding sequences.
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- 2022
6. Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer
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Lee, Joyce V, Housley, Filomena, Yau, Christina, Nakagawa, Rachel, Winkler, Juliane, Anttila, Johanna M, Munne, Pauliina M, Savelius, Mariel, Houlahan, Kathleen E, Van de Mark, Daniel, Hemmati, Golzar, Hernandez, Grace A, Zhang, Yibing, Samson, Susan, Baas, Carole, Kok, Marleen, Esserman, Laura J, van ‘t Veer, Laura J, Rugo, Hope S, Curtis, Christina, Klefström, Juha, Matloubian, Mehrdad, and Goga, Andrei
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Vaccine Related ,Cancer ,Breast Cancer ,Immunization ,Animals ,B7-H1 Antigen ,Humans ,Immune Checkpoint Inhibitors ,Immune Evasion ,Immunotherapy ,Mice ,Proto-Oncogene Proteins c-myc ,Signal Transduction ,Triple Negative Breast Neoplasms - Abstract
Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors.
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- 2022
7. Copy Number Profiles of Prostate Cancer in Men of Middle Eastern Ancestry.
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Albawardi, Alia, Livingstone, Julie, Almarzooqi, Saeeda, Palanisamy, Nallasivam, Houlahan, Kathleen E, Awwad, Aktham Adnan Ahmad, Abdelsalam, Ramy A, Boutros, Paul C, and Bismar, Tarek A
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copy number aberrations ,middle eastern ancestry ,prostate cancer ,Aging ,Genetics ,Human Genome ,Prostate Cancer ,Cancer ,Urologic Diseases ,Biotechnology ,Oncology and Carcinogenesis - Abstract
Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of genome-wide copy number profiles of 401 tumors of all ancestries. FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (2.3%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 × 10-3). Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those in men of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (two-sided proportion test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ motif-containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Larger studies investigating ME populations are warranted to confirm these observations.
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- 2021
8. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer.
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Ahmed, Musaddeque, Soares, Fraser, Xia, Ji-Han, Yang, Yue, Li, Jing, Guo, Haiyang, Su, Peiran, Tian, Yijun, Lee, Hyung Joo, Wang, Miranda, Akhtar, Nayeema, Houlahan, Kathleen E, Bosch, Almudena, Zhou, Stanley, Mazrooei, Parisa, Hua, Junjie T, Chen, Sujun, Petricca, Jessica, Zeng, Yong, Davies, Alastair, Fraser, Michael, Quigley, David A, Feng, Felix Y, Boutros, Paul C, Lupien, Mathieu, Zoubeidi, Amina, Wang, Liang, Walsh, Martin J, Wang, Ting, Ren, Shancheng, Wei, Gong-Hong, and He, Housheng Hansen
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Cell Line ,Tumor ,Animals ,Mice ,Inbred NOD ,Humans ,Mice ,SCID ,Prostatic Neoplasms ,Genetic Predisposition to Disease ,Proto-Oncogene Proteins c-myc ,Risk Factors ,DNA Methylation ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Male ,Regulatory Elements ,Transcriptional ,Promoter Regions ,Genetic ,Genome-Wide Association Study ,Carcinogenesis ,CRISPR-Cas Systems ,Gene Editing ,CCCTC-Binding Factor ,Human Genome ,Aging ,Prostate Cancer ,Urologic Diseases ,Cancer ,Genetics ,2.1 Biological and endogenous factors - Abstract
Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.
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- 2021
9. The DNA methylation landscape of advanced prostate cancer
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Zhao, Shuang G, Chen, William S, Li, Haolong, Foye, Adam, Zhang, Meng, Sjöström, Martin, Aggarwal, Rahul, Playdle, Denise, Liao, Arnold, Alumkal, Joshi J, Das, Rajdeep, Chou, Jonathan, Hua, Junjie T, Barnard, Travis J, Bailey, Adina M, Chow, Eric D, Perry, Marc D, Dang, Ha X, Yang, Rendong, Moussavi-Baygi, Ruhollah, Zhang, Li, Alshalalfa, Mohammed, Laura Chang, S, Houlahan, Kathleen E, Shiah, Yu-Jia, Beer, Tomasz M, Thomas, George, Chi, Kim N, Gleave, Martin, Zoubeidi, Amina, Reiter, Robert E, Rettig, Matthew B, Witte, Owen, Yvonne Kim, M, Fong, Lawrence, Spratt, Daniel E, Morgan, Todd M, Bose, Rohit, Huang, Franklin W, Li, Hui, Chesner, Lisa, Shenoy, Tanushree, Goodarzi, Hani, Asangani, Irfan A, Sandhu, Shahneen, Lang, Joshua M, Mahajan, Nupam P, Lara, Primo N, Evans, Christopher P, Febbo, Phillip, Batzoglou, Serafim, Knudsen, Karen E, He, Housheng H, Huang, Jiaoti, Zwart, Wilbert, Costello, Joseph F, Luo, Jianhua, Tomlins, Scott A, Wyatt, Alexander W, Dehm, Scott M, Ashworth, Alan, Gilbert, Luke A, Boutros, Paul C, Farh, Kyle, Chinnaiyan, Arul M, Maher, Christopher A, Small, Eric J, Quigley, David A, and Feng, Felix Y
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Cancer ,Prostate Cancer ,Human Genome ,Urologic Diseases ,Cancer Genomics ,Biotechnology ,2.1 Biological and endogenous factors ,Aged ,Aged ,80 and over ,Carcinogenesis ,DNA Methylation ,Epigenomics ,Gene Expression Regulation ,Neoplastic ,Genome ,Humans ,Male ,Middle Aged ,Mutation ,Prospective Studies ,Prostatic Neoplasms ,Sequence Analysis ,DNA ,Exome Sequencing ,Whole Genome Sequencing ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.
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- 2020
10. The landscape of RNA polymerase II associated chromatin interactions in prostate cancer
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Ramanand, Susmita G, Chen, Yong, Yuan, Jiapei, Daescu, Kelly, Lambros, Maryou, Houlahan, Kathleen E, Carreira, Suzanne, Yuan, Wei, Baek, GuemHee, Sharp, Adam, Paschalis, Alec, Kanchwala, Mohammed, Gao, Yunpeng, Aslam, Adam, Safdar, Nida, Zhan, Xiaowei, Raj, Ganesh V, Xing, Chao, Boutros, Paul C, de Bono, Johann, Zhang, Michael Q, and Mani, Ram S
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Prostate Cancer ,Urologic Diseases ,Aging ,Genetics ,Human Genome ,Cancer ,Underpinning research ,1.1 Normal biological development and functioning ,Biomarkers ,Tumor ,Cell Line ,Tumor ,Chromatin ,Gene Expression Regulation ,Neoplastic ,Humans ,Male ,Neoplasm Proteins ,Prostatic Neoplasms ,RNA Polymerase II ,Response Elements ,Epigenetics ,Oncology ,Prostate cancer ,Transcription ,Medical and Health Sciences ,Immunology - Abstract
Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprising the AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, ZBTB16), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes - VPS53, FAM57A, and GEMIN4. Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa.
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- 2020
11. BPG: Seamless, automated and interactive visualization of scientific data
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P’ng, Christine, Green, Jeffrey, Chong, Lauren C, Waggott, Daryl, Prokopec, Stephenie D, Shamsi, Mehrdad, Nguyen, Francis, Mak, Denise YF, Lam, Felix, Albuquerque, Marco A, Wu, Ying, Jung, Esther H, Starmans, Maud HW, Chan-Seng-Yue, Michelle A, Yao, Cindy Q, Liang, Bianca, Lalonde, Emilie, Haider, Syed, Simone, Nicole A, Sendorek, Dorota, Chu, Kenneth C, Moon, Nathalie C, Fox, Natalie S, Grzadkowski, Michal R, Harding, Nicholas J, Fung, Clement, Murdoch, Amanda R, Houlahan, Kathleen E, Wang, Jianxin, Garcia, David R, de Borja, Richard, Sun, Ren X, Lin, Xihui, Chen, Gregory M, Lu, Aileen, Shiah, Yu-Jia, Zia, Amin, Kearns, Ryan, and Boutros, Paul C
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Information and Computing Sciences ,Applied Computing ,Networking and Information Technology R&D (NITRD) ,Data Analysis ,Humans ,Simulation Training ,Software ,Data-visualization ,Interactive plotting ,Web-resources ,Mathematical Sciences ,Biological Sciences ,Bioinformatics ,Biological sciences ,Information and computing sciences ,Mathematical sciences - Abstract
BackgroundWe introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment.ResultsThis open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines.ConclusionBPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.
- Published
- 2019
12. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts
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Strand, Siri H., Rivero-Gutiérrez, Belén, Houlahan, Kathleen E., Seoane, Jose A., King, Lorraine M., Risom, Tyler, Simpson, Lunden A., Vennam, Sujay, Khan, Aziz, Cisneros, Luis, Hardman, Timothy, Harmon, Bryan, Couch, Fergus, Gallagher, Kristalyn, Kilgore, Mark, Wei, Shi, DeMichele, Angela, King, Tari, McAuliffe, Priscilla F., Nangia, Julie, Lee, Joanna, Tseng, Jennifer, Storniolo, Anna Maria, Thompson, Alastair M., Gupta, Gaorav P., Burns, Robyn, Veis, Deborah J., DeSchryver, Katherine, Zhu, Chunfang, Matusiak, Magdalena, Wang, Jason, Zhu, Shirley X., Tappenden, Jen, Ding, Daisy Yi, Zhang, Dadong, Luo, Jingqin, Jiang, Shu, Varma, Sushama, Anderson, Lauren, Straub, Cody, Srivastava, Sucheta, Curtis, Christina, Tibshirani, Rob, Angelo, Robert Michael, Hall, Allison, Owzar, Kouros, Polyak, Kornelia, Maley, Carlo, Marks, Jeffrey R., Colditz, Graham A., Hwang, E. Shelley, and West, Robert B.
- Published
- 2022
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13. Genome-wide germline correlates of the epigenetic landscape of prostate cancer
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Houlahan, Kathleen E, Shiah, Yu-Jia, Gusev, Alexander, Yuan, Jiapei, Ahmed, Musaddeque, Shetty, Anamay, Ramanand, Susmita G, Yao, Cindy Q, Bell, Connor, O’Connor, Edward, Huang, Vincent, Fraser, Michael, Heisler, Lawrence E, Livingstone, Julie, Yamaguchi, Takafumi N, Rouette, Alexandre, Foucal, Adrien, Espiritu, Shadrielle Melijah G, Sinha, Ankit, Sam, Michelle, Timms, Lee, Johns, Jeremy, Wong, Ada, Murison, Alex, Orain, Michèle, Picard, Valérie, Hovington, Hélène, Bergeron, Alain, Lacombe, Louis, Lupien, Mathieu, Fradet, Yves, Têtu, Bernard, McPherson, John D, Pasaniuc, Bogdan, Kislinger, Thomas, Chua, Melvin LK, Pomerantz, Mark M, van der Kwast, Theodorus, Freedman, Matthew L, Mani, Ram S, He, Housheng H, Bristow, Robert G, and Boutros, Paul C
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Urologic Diseases ,Genetics ,Aging ,Cancer ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,DNA Methylation ,Epigenome ,Gene Expression Profiling ,Gene Expression Regulation ,Neoplastic ,Genetic Predisposition to Disease ,Genome ,Human ,Germ-Line Mutation ,Humans ,Male ,Neoplasm Recurrence ,Local ,Prostatic Neoplasms ,Proto-Oncogene Proteins c-akt ,Quantitative Trait Loci ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
Oncogenesis is driven by germline, environmental and stochastic factors. It is unknown how these interact to produce the molecular phenotypes of tumors. We therefore quantified the influence of germline polymorphisms on the somatic epigenome of 589 localized prostate tumors. Predisposition risk loci influence a tumor's epigenome, uncovering a mechanism for cancer susceptibility. We identified and validated 1,178 loci associated with altered methylation in tumoral but not nonmalignant tissue. These tumor methylation quantitative trait loci influence chromatin structure, as well as RNA and protein abundance. One prominent tumor methylation quantitative trait locus is associated with AKT1 expression and is predictive of relapse after definitive local therapy in both discovery and validation cohorts. These data reveal intricate crosstalk between the germ line and the epigenome of primary tumors, which may help identify germline biomarkers of aggressive disease to aid patient triage and optimize the use of more invasive or expensive diagnostic assays.
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- 2019
14. Modelling the MYC-driven normal-to-tumour switch in breast cancer.
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Lourenco, Corey, Kalkat, Manpreet, Houlahan, Kathleen E, De Melo, Jason, Longo, Joseph, Done, Susan J, Boutros, Paul C, and Penn, Linda Z
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Breast ,Cell Line ,Tumor ,Humans ,Breast Neoplasms ,Cell Transformation ,Neoplastic ,Neoplasm Invasiveness ,Signal Transduction ,Gene Expression Regulation ,Neoplastic ,Genes ,myc ,Models ,Biological ,Female ,Phosphatidylinositol 3-Kinases ,Breast cancer ,Cancer model ,Driver oncogene ,MYC ,Microenvironment ,PI3K ,Cell Line ,Tumor ,Cell Transformation ,Neoplastic ,Gene Expression Regulation ,Genes ,myc ,Models ,Biological ,Developmental Biology ,Biological Sciences ,Medical and Health Sciences - Abstract
The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CAH1047R) led to the development of organised acinar structures in mice. Expressing both PIK3CAH1047R and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay in vivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.
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- 2019
15. Molecular Hallmarks of Multiparametric Magnetic Resonance Imaging Visibility in Prostate Cancer
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Houlahan, Kathleen E, Salmasi, Amirali, Sadun, Taylor Y, Pooli, Aydin, Felker, Ely R, Livingstone, Julie, Huang, Vincent, Raman, Steven S, Ahuja, Preeti, Sisk, Anthony E, Boutros, Paul C, and Reiter, Robert E
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Aging ,Urologic Diseases ,Cancer ,Biomedical Imaging ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Aged ,Gene Dosage ,Gene Expression Profiling ,Genome ,Humans ,Male ,Middle Aged ,Multiparametric Magnetic Resonance Imaging ,Prostatic Neoplasms ,RNA ,Long Noncoding ,RNA ,Messenger ,RNA ,Small Nuclear ,Transcriptome ,Tumor Burden ,Tumor Microenvironment ,Prostate cancer ,Multiparametric magnetic resonance imaging visibility ,Radiogenomics ,Nimbosus ,Transcriptomics ,Urology & Nephrology ,Clinical sciences - Abstract
Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2
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- 2019
16. BPG: Seamless, automated and interactive visualization of scientific data.
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P'ng, Christine, Green, Jeffrey, Chong, Lauren C, Waggott, Daryl, Prokopec, Stephenie D, Shamsi, Mehrdad, Nguyen, Francis, Mak, Denise YF, Lam, Felix, Albuquerque, Marco A, Wu, Ying, Jung, Esther H, Starmans, Maud HW, Chan-Seng-Yue, Michelle A, Yao, Cindy Q, Liang, Bianca, Lalonde, Emilie, Haider, Syed, Simone, Nicole A, Sendorek, Dorota, Chu, Kenneth C, Moon, Nathalie C, Fox, Natalie S, Grzadkowski, Michal R, Harding, Nicholas J, Fung, Clement, Murdoch, Amanda R, Houlahan, Kathleen E, Wang, Jianxin, Garcia, David R, de Borja, Richard, Sun, Ren X, Lin, Xihui, Chen, Gregory M, Lu, Aileen, Shiah, Yu-Jia, Zia, Amin, Kearns, Ryan, and Boutros, Paul C
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Humans ,Software ,Simulation Training ,Data Analysis ,Data-visualization ,Interactive plotting ,Web-resources ,Networking and Information Technology R&D ,Biological Sciences ,Information and Computing Sciences ,Mathematical Sciences ,Bioinformatics - Abstract
BackgroundWe introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment.ResultsThis open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines.ConclusionBPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.
- Published
- 2019
17. PLATYPUS: A Multiple-View Learning Predictive Framework for Cancer Drug Sensitivity Prediction.
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Graim, Kiley, Friedl, Verena, Houlahan, Kathleen E, and Stuart, Joshua M
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Biological Sciences ,Bioinformatics and Computational Biology ,Cancer ,8.4 Research design and methodologies (health services) ,Health and social care services research ,Good Health and Well Being ,Antineoplastic Agents ,Cell Line ,Tumor ,Computational Biology ,Databases ,Factual ,Drug Resistance ,Neoplasm ,Humans ,Information Storage and Retrieval ,Machine Learning ,Neoplasms ,Patient-Specific Modeling ,Pharmacogenomic Variants ,Precision Medicine ,Software ,Supervised Machine Learning ,Pattern Recognition ,Multiple View Learning ,Drug Sensitivity ,Incompleteness ,Unlabeled Data ,Semi-Supervised ,Co-Training ,Integrative Genomics ,Systems Biology ,Multidimensional ,Multi-Omic - Abstract
Cancer is a complex collection of diseases that are to some degree unique to each patient. Precision oncology aims to identify the best drug treatment regime using molecular data on tumor samples. While omics-level data is becoming more widely available for tumor specimens, the datasets upon which computational learning methods can be trained vary in coverage from sample to sample and from data type to data type. Methods that can 'connect the dots' to leverage more of the information provided by these studies could offer major advantages for maximizing predictive potential. We introduce a multi-view machinelearning strategy called PLATYPUS that builds 'views' from multiple data sources that are all used as features for predicting patient outcomes. We show that a learning strategy that finds agreement across the views on unlabeled data increases the performance of the learning methods over any single view. We illustrate the power of the approach by deriving signatures for drug sensitivity in a large cancer cell line database. Code and additional information are available from the PLATYPUS website https://sysbiowiki.soe.ucsc.edu/platypus.
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- 2019
18. Germline contamination and leakage in whole genome somatic single nucleotide variant detection
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Sendorek, Dorota H, Caloian, Cristian, Ellrott, Kyle, Bare, J Christopher, Yamaguchi, Takafumi N, Ewing, Adam D, Houlahan, Kathleen E, Norman, Thea C, Margolin, Adam A, Stuart, Joshua M, and Boutros, Paul C
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Cancer ,Generic health relevance ,Good Health and Well Being ,Algorithms ,Genome ,Human ,Germ Cells ,Humans ,Internet ,Neoplasms ,Polymorphism ,Single Nucleotide ,User-Computer Interface ,Whole Genome Sequencing ,Cancer genomics ,Next-generation sequencing ,Mutation calling ,Germline contamination ,Germline leakage ,Patient identifiability ,Single nucleotide variant ,SNV ,Mathematical Sciences ,Information and Computing Sciences ,Bioinformatics ,Biological sciences ,Information and computing sciences ,Mathematical sciences - Abstract
BackgroundThe clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge.ResultsThe median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases.ConclusionsThe potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.
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- 2018
19. Valection: design optimization for validation and verification studies
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Cooper, Christopher I, Yao, Delia, Sendorek, Dorota H, Yamaguchi, Takafumi N, P’ng, Christine, Houlahan, Kathleen E, Caloian, Cristian, Fraser, Michael, SMC-DNA Challenge Participants, Ellrott, Kyle, Margolin, Adam A, Bristow, Robert G, Stuart, Joshua M, and Boutros, Paul C
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Sequence Analysis ,DNA ,Software Validation ,Verification ,Validation ,Candidate-selection ,DNA sequencing ,SMC-DNA Challenge Participants ,Mathematical Sciences ,Biological Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundPlatform-specific error profiles necessitate confirmatory studies where predictions made on data generated using one technology are additionally verified by processing the same samples on an orthogonal technology. However, verifying all predictions can be costly and redundant, and testing a subset of findings is often used to estimate the true error profile.ResultsTo determine how to create subsets of predictions for validation that maximize accuracy of global error profile inference, we developed Valection, a software program that implements multiple strategies for the selection of verification candidates. We evaluated these selection strategies on one simulated and two experimental datasets.ConclusionsValection is implemented in multiple programming languages, available at: http://labs.oicr.on.ca/boutros-lab/software/valection.
- Published
- 2018
20. Combining accurate tumor genome simulation with crowdsourcing to benchmark somatic structural variant detection
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Lee, Anna Y, Ewing, Adam D, Ellrott, Kyle, Hu, Yin, Houlahan, Kathleen E, Bare, J Christopher, Espiritu, Shadrielle Melijah G, Huang, Vincent, Dang, Kristen, Chong, Zechen, Caloian, Cristian, Yamaguchi, Takafumi N, Kellen, Michael R, Chen, Ken, Norman, Thea C, Friend, Stephen H, Guinney, Justin, Stolovitzky, Gustavo, Haussler, David, Margolin, Adam A, Stuart, Joshua M, and Boutros, Paul C
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Biological Sciences ,Biomedical and Clinical Sciences ,Bioinformatics and Computational Biology ,Genetics ,Oncology and Carcinogenesis ,Cancer ,Human Genome ,Generic health relevance ,Algorithms ,Benchmarking ,Computer Simulation ,Crowdsourcing ,Databases ,Genetic ,Genetic Variation ,Genome ,Human ,Genomics ,High-Throughput Nucleotide Sequencing ,Humans ,Neoplasms ,Software ,Somatic mutations ,Simulation ,Structural variants ,Cancer genomics ,Whole-genome sequencing ,ICGC-TCGA DREAM Somatic Mutation Calling Challenge Participants ,Environmental Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundThe phenotypes of cancer cells are driven in part by somatic structural variants. Structural variants can initiate tumors, enhance their aggressiveness, and provide unique therapeutic opportunities. Whole-genome sequencing of tumors can allow exhaustive identification of the specific structural variants present in an individual cancer, facilitating both clinical diagnostics and the discovery of novel mutagenic mechanisms. A plethora of somatic structural variant detection algorithms have been created to enable these discoveries; however, there are no systematic benchmarks of them. Rigorous performance evaluation of somatic structural variant detection methods has been challenged by the lack of gold standards, extensive resource requirements, and difficulties arising from the need to share personal genomic information.ResultsTo facilitate structural variant detection algorithm evaluations, we create a robust simulation framework for somatic structural variants by extending the BAMSurgeon algorithm. We then organize and enable a crowdsourced benchmarking within the ICGC-TCGA DREAM Somatic Mutation Calling Challenge (SMC-DNA). We report here the results of structural variant benchmarking on three different tumors, comprising 204 submissions from 15 teams. In addition to ranking methods, we identify characteristic error profiles of individual algorithms and general trends across them. Surprisingly, we find that ensembles of analysis pipelines do not always outperform the best individual method, indicating a need for new ways to aggregate somatic structural variant detection approaches.ConclusionsThe synthetic tumors and somatic structural variant detection leaderboards remain available as a community benchmarking resource, and BAMSurgeon is available at https://github.com/adamewing/bamsurgeon .
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- 2018
21. Author Correction: Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer
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Lee, Joyce V., Housley, Filomena, Yau, Christina, Nakagawa, Rachel, Winkler, Juliane, Anttila, Johanna M., Munne, Pauliina M., Savelius, Mariel, Houlahan, Kathleen E., Van de Mark, Daniel, Hemmati, Golzar, Hernandez, Grace A., Zhang, Yibing, Samson, Susan, Baas, Carole, Kok, Marleen, Esserman, Laura J., van ‘t Veer, Laura J., Rugo, Hope S., Curtis, Christina, Klefström, Juha, Matloubian, Mehrdad, and Goga, Andrei
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- 2022
- Full Text
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22. MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability.
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Dingar, Dharmendra, Tu, William B, Resetca, Diana, Lourenco, Corey, Tamachi, Aaliya, De Melo, Jason, Houlahan, Kathleen E, Kalkat, Manpreet, Chan, Pak-Kei, Boutros, Paul C, Raught, Brian, and Penn, Linda Z
- Subjects
Cell Line ,Tumor ,Chromatin ,Humans ,RNA-Binding Proteins ,DNA-Binding Proteins ,Proto-Oncogene Proteins c-myc ,Nuclear Proteins ,Immunoblotting ,Electrophoresis ,Gel ,Two-Dimensional ,Chromatin Immunoprecipitation ,Immunoprecipitation ,Mass Spectrometry ,Protein Phosphatase 1 ,Protein Stability ,Cell Line ,Tumor ,Electrophoresis ,Gel ,Two-Dimensional ,Biotechnology ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Generic Health Relevance - Abstract
The c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC interactome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCFFBXW7 pathway. MYC hyperphosphorylation can be rescued specifically with exogenous PP1, but not other phosphatases. Hyperphosphorylated MYC retained interaction with its transcriptional partner MAX, but binding to chromatin is significantly compromised. Our work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells.
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- 2018
23. Pathogenic Germline Variants in 10,389 Adult Cancers
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Huang, Kuan-lin, Mashl, R Jay, Wu, Yige, Ritter, Deborah I, Wang, Jiayin, Oh, Clara, Paczkowska, Marta, Reynolds, Sheila, Wyczalkowski, Matthew A, Oak, Ninad, Scott, Adam D, Krassowski, Michal, Cherniack, Andrew D, Houlahan, Kathleen E, Jayasinghe, Reyka, Wang, Liang-Bo, Zhou, Daniel Cui, Liu, Di, Cao, Song, Kim, Young Won, Koire, Amanda, McMichael, Joshua F, Hucthagowder, Vishwanathan, Kim, Tae-Beom, Hahn, Abigail, Wang, Chen, McLellan, Michael D, Al-Mulla, Fahd, Johnson, Kimberly J, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, and Gao, Jianjiong
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Prevention ,Cancer Genomics ,Human Genome ,2.1 Biological and endogenous factors ,DNA Copy Number Variations ,Databases ,Genetic ,Gene Deletion ,Gene Frequency ,Genetic Predisposition to Disease ,Genotype ,Germ Cells ,Germ-Line Mutation ,Humans ,Loss of Heterozygosity ,Mutation ,Missense ,Neoplasms ,Polymorphism ,Single Nucleotide ,Proto-Oncogene Proteins c-met ,Proto-Oncogene Proteins c-ret ,Tumor Suppressor Proteins ,Cancer Genome Atlas Research Network ,LOH ,cancer predisposition ,germline and somatic genomes ,variant pathogenicity ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer.
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- 2018
24. Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems
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Prokopec, Stephenie D, Houlahan, Kathleen E, Sun, Ren X, Watson, John D, Yao, Cindy Q, Lee, Jamie, P’ng, Christine, Pang, Renee, Wu, Alexander H, Chong, Lauren C, Smith, Ashley B, Harding, Nicholas J, Moffat, Ivy D, Lindén, Jere, Lensu, Sanna, Okey, Allan B, Pohjanvirta, Raimo, and Boutros, Paul C
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Biological Sciences ,Biomedical and Clinical Sciences ,Agent Orange & Dioxin ,Genetics ,Animals ,Cell Line ,Computational Biology ,Environmental Pollutants ,Female ,Gene Expression Profiling ,Gene Expression Regulation ,Humans ,Male ,Mice ,Polychlorinated Dibenzodioxins ,Rats ,Software ,Transcriptome ,Web Browser ,TCDD ,AHR ,Microarray datasets ,R ,Information and Computing Sciences ,Medical and Health Sciences ,Bioinformatics ,Biological sciences ,Biomedical and clinical sciences - Abstract
Background2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR.ResultsSpecifically, we have created a datasets package - TCDD.Transcriptomics - for the R statistical environment, consisting of 63 unique experiments comprising 377 samples, including various combinations of 3 species (human derived cell lines, mouse and rat), 4 tissue types (liver, kidney, white adipose tissue and hypothalamus) and a wide range of TCDD exposure times and doses. These datasets have been fully standardized using consistent preprocessing and annotation packages (available as of September 14, 2015). To demonstrate the utility of this R package, a subset of "AHR-core" genes were evaluated across the included datasets. Ahrr, Nqo1 and members of the Cyp family were significantly induced following exposure to TCDD across the studies as expected while Aldh3a1 was induced specifically in rat liver. Inmt was altered only in liver tissue and primarily by rat-AHR.ConclusionsAnalysis of the "AHR-core" genes demonstrates a continued need for studies surrounding the impact of AHR-activity on the transcriptome; genes believed to be consistently regulated by ligand-activated AHR show surprisingly little overlap across species and tissues. Until now, a comprehensive assessment of the transcriptome across these studies was challenging due to differences in array platforms, processing methods and annotation versions. We believe that this package, which is freely available for download ( http://labs.oicr.on.ca/boutros-lab/tcdd-transcriptomics ) will prove to be a highly beneficial resource to the scientific community evaluating the effects of TCDD exposure as well as the variety of functions of the AHR.
- Published
- 2017
25. Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection
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Ewing, Adam D, Houlahan, Kathleen E, Hu, Yin, Ellrott, Kyle, Caloian, Cristian, Yamaguchi, Takafumi N, Bare, J Christopher, P'ng, Christine, Waggott, Daryl, Sabelnykova, Veronica Y, Kellen, Michael R, Norman, Thea C, Haussler, David, Friend, Stephen H, Stolovitzky, Gustavo, Margolin, Adam A, Stuart, Joshua M, and Boutros, Paul C
- Subjects
Genetics ,Cancer ,Human Genome ,Algorithms ,Benchmarking ,Crowdsourcing ,Genome ,Humans ,Neoplasms ,Polymorphism ,Single Nucleotide ,ICGC-TCGA DREAM Somatic Mutation Calling Challenge participants ,Biological Sciences ,Technology ,Medical and Health Sciences ,Developmental Biology - Abstract
The detection of somatic mutations from cancer genome sequences is key to understanding the genetic basis of disease progression, patient survival and response to therapy. Benchmarking is needed for tool assessment and improvement but is complicated by a lack of gold standards, by extensive resource requirements and by difficulties in sharing personal genomic information. To resolve these issues, we launched the ICGC-TCGA DREAM Somatic Mutation Calling Challenge, a crowdsourced benchmark of somatic mutation detection algorithms. Here we report the BAMSurgeon tool for simulating cancer genomes and the results of 248 analyses of three in silico tumors created with it. Different algorithms exhibit characteristic error profiles, and, intriguingly, false positives show a trinucleotide profile very similar to one found in human tumors. Although the three simulated tumors differ in sequence contamination (deviation from normal cell sequence) and in subclonality, an ensemble of pipelines outperforms the best individual pipeline in all cases. BAMSurgeon is available at https://github.com/adamewing/bamsurgeon/.
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- 2015
26. Cross-species transcriptomic analysis elucidates constitutive aryl hydrocarbon receptor activity.
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Sun, Ren X, Chong, Lauren C, Simmons, Trent T, Houlahan, Kathleen E, Prokopec, Stephenie D, Watson, John D, Moffat, Ivy D, Lensu, Sanna, Lindén, Jere, P'ng, Christine, Okey, Allan B, Pohjanvirta, Raimo, and Boutros, Paul C
- Subjects
Animals ,Mice ,Rats ,Receptors ,Aryl Hydrocarbon ,Cluster Analysis ,Gene Expression Profiling ,Computational Biology ,Signal Transduction ,Organ Specificity ,Species Specificity ,Gene Expression Regulation ,Protein Binding ,Male ,Transcriptome ,Aryl hydrocarbon receptor ,AHR endogenous ligands ,Constitutive gene expression ,TCDD-induced toxicity ,Core-gene battery ,Receptors ,Aryl Hydrocarbon ,Biological Sciences ,Information and Computing Sciences ,Medical and Health Sciences ,Bioinformatics - Abstract
BackgroundResearch on the aryl hydrocarbon receptor (AHR) has largely focused on variations in toxic outcomes resulting from its activation by halogenated aromatic hydrocarbons. But the AHR also plays key roles in regulating pathways critical for development, and after decades of research the mechanisms underlying physiological regulation by the AHR remain poorly characterized. Previous studies identified several core genes that respond to xenobiotic AHR ligands across a broad range of species and tissues. However, only limited inferences have been made regarding its role in regulating constitutive gene activity, i.e. in the absence of exogenous ligands. To address this, we profiled transcriptomic variations between AHR-active and AHR-less-active animals in the absence of an exogenous agonist across five tissues, three of which came from rats (hypothalamus, white adipose and liver) and two of which came from mice (kidney and liver). Because AHR status alone has been shown sufficient to alter transcriptomic responses, we reason that by contrasting profiles amongst AHR-variant animals, we may elucidate effects of the AHR on constitutive mRNA abundances.ResultsWe found significantly more overlap in constitutive mRNA abundances amongst tissues within the same species than from tissues between species and identified 13 genes (Agt, Car3, Creg1, Ctsc, E2f6, Enpp1, Gatm, Gstm4, Kcnj8, Me1, Pdk1, Slc35a3, and Sqrdl) that are affected by AHR-status in four of five tissues. One gene, Creg1, was significantly up-regulated in all AHR-less-active animals. We also find greater overlap between tissues at the pathway level than at the gene level, suggesting coherency to the AHR signalling response within these processes. Analysis of regulatory motifs suggests that the AHR mostly mediates transcriptional regulation via direct binding to response elements.ConclusionsThese findings, though preliminary, present a platform for further evaluating the role of the AHR in regulation of constitutive mRNA levels and physiologic function.
- Published
- 2014
27. Analysis of ductal carcinoma in situ by self-reported race reveals molecular differences related to outcome
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Strand, Siri H., primary, Houlahan, Kathleen E., additional, Branch, Vernal, additional, Lynch, Thomas, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla, additional, Curtis, Christina, additional, Owzar, Kouros, additional, Marks, Jeffrey R., additional, Colditz, Graham A., additional, Hwang, E. Shelley, additional, and West, Robert B., additional
- Published
- 2023
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- View/download PDF
28. Deterministic evolution and stringent selection during preneoplasia
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Karlsson, Kasper, primary, Przybilla, Moritz J., additional, Kotler, Eran, additional, Khan, Aziz, additional, Xu, Hang, additional, Karagyozova, Kremena, additional, Sockell, Alexandra, additional, Wong, Wing H., additional, Liu, Katherine, additional, Mah, Amanda, additional, Lo, Yuan-Hung, additional, Lu, Bingxin, additional, Houlahan, Kathleen E., additional, Ma, Zhicheng, additional, Suarez, Carlos J., additional, Barnes, Chris P., additional, Kuo, Calvin J., additional, and Curtis, Christina, additional
- Published
- 2023
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29. Abstract 3315: Evaluating biomarker potential of germline genomic factors for predicting clinical outcomes in prostate cancer
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Zeltser, Nicole, primary, Houlahan, Kathleen E., additional, Al-Hiyari, Sarah M., additional, Eng, Stefan E., additional, Patel, Yash, additional, Yamaguchi, Takafumi N., additional, Tao, Shu, additional, Huang, Rong Rong, additional, Reiter, Robert E., additional, Ye, Huihui, additional, Kinnaird, Adam S., additional, and Boutros, Paul C., additional
- Published
- 2023
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30. Abstract 4305: Germline structural variants shape prostate cancer clinical and molecular evolution
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Wang, Nicholas K., primary, Rouette, Alexandre, additional, Houlahan, Kathleen E., additional, Yamaguchi, Takafumi N., additional, Livingstone, Julie, additional, Jung, Chol-Hee, additional, Georgeson, Peter, additional, Fraser, Michael, additional, Shiah, Yu-Jia, additional, Yao, Cindy Q., additional, Huang, Vincent, additional, Fox, Natalie S., additional, Kurganovs, Natalie, additional, Kasaian, Katayoon, additional, Sabelnykova, Veronica Y., additional, Jayalath, Jay, additional, Weke, Kenneth, additional, Zhu, Helen, additional, van der Kwast, Theodorus, additional, Papenfuss, Tony, additional, He, Housheng H., additional, Corcoran, Niall M., additional, Bristow, Robert G., additional, Zlotta, Alexandre R., additional, Hovens, Christopher, additional, and Boutros, Paul C., additional
- Published
- 2023
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31. Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity
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Houlahan, Kathleen E, primary, Khan, Aziz, additional, Greenwald, Noah F, additional, West, Robert B, additional, Angelo, Michael, additional, and Curtis, Christina, additional
- Published
- 2023
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32. A polygenic two-hit hypothesis for prostate cancer
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Houlahan, Kathleen E, primary, Livingstone, Julie, additional, Fox, Natalie S, additional, Kurganovs, Natalie, additional, Zhu, Helen, additional, Sietsma Penington, Jocelyn, additional, Jung, Chol-Hee, additional, Yamaguchi, Takafumi N, additional, Heisler, Lawrence E, additional, Jovelin, Richard, additional, Costello, Anthony J, additional, Pope, Bernard J, additional, Kishan, Amar U, additional, Corcoran, Niall M, additional, Bristow, Robert G, additional, Waszak, Sebastian M, additional, Weischenfeldt, Joachim, additional, He, Housheng H, additional, Hung, Rayjean J, additional, Hovens, Christopher M, additional, and Boutros, Paul C, additional
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- 2023
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33. Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin
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Houlahan, Kathleen E., Prokopec, Stephenie D., Moffat, Ivy D., Lindén, Jere, Lensu, Sanna, Okey, Allan B., Pohjanvirta, Raimo, and Boutros, Paul C.
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- 2015
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34. Germline determinants of the prostate tumor genome
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Houlahan, Kathleen E., primary, Yuan, Jiapei, additional, Schwarz, Tommer, additional, Livingstone, Julie, additional, Fox, Natalie S., additional, Jaratlerdsiri, Weerachai, additional, van Riet, Job, additional, Taraszka, Kodi, additional, Kurganovs, Natalie, additional, Zhu, Helen, additional, Sietsma Penington, Jocelyn, additional, Jung, Chol-Hee, additional, Yamaguchi, Takafumi N, additional, Jiang, Jue, additional, Heisler, Lawrence E, additional, Jovelin, Richard, additional, Ramanand, Susmita G, additional, Bell, Connor, additional, O’Connor, Edward, additional, Mutambirwa, Shingai B.A., additional, Seo, Ji-Heui, additional, Costello, Anthony J., additional, Pomerantz, Mark M., additional, Pope, Bernard J., additional, Zaitlen, Noah, additional, Kishan, Amar U., additional, Corcoran, Niall M., additional, Bristow, Robert G., additional, Waszak, Sebastian M., additional, Bornman, Riana M.S., additional, Gusev, Alexander, additional, Lolkema, Martijn P., additional, Weischenfeldt, Joachim, additional, Hung, Rayjean J., additional, He, Housheng H., additional, Hayes, Vanessa M., additional, Pasaniuc, Bogdan, additional, Freedman, Matthew L., additional, Hovens, Christopher M., additional, Mani, Ram S., additional, and Boutros, Paul C., additional
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- 2022
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35. Gene Therapy
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Houlahan, Kathleen E., Kierancr, Mark W., Tomlinson, Deborah, editor, and Kline, Nancy E., editor
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- 2005
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36. Genomic hallmarks of localized, non-indolent prostate cancer
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Fraser, Michael, Sabelnykova, Veronica Y., Yamaguchi, Takafumi N., Heisler, Lawrence E., Livingstone, Julie, Huang, Vincent, Shiah, Yu-Jia, Yousif, Fouad, Lin, Xihui, Masella, Andre P., Fox, Natalie S., Xie, Michael, Prokopec, Stephenie D., Berlin, Alejandro, Lalonde, Emilie, Ahmed, Musaddeque, Trudel, Dominique, Luo, Xuemei, Beck, Timothy A., Meng, Alice, Zhang, Junyan, DʼCosta, Alister, Denroche, Robert E., Kong, Haiying, Espiritu, Shadrielle Melijah G., Chua, Melvin L. K., Wong, Ada, Chong, Taryne, Sam, Michelle, Johns, Jeremy, Timms, Lee, Buchner, Nicholas B., Orain, Michèle, Picard, Valérie, Hovington, Helène, Murison, Alexander, Kron, Ken, Harding, Nicholas J., Pʼng, Christine, Houlahan, Kathleen E., Chu, Kenneth C., Lo, Bryan, Nguyen, Francis, Li, Constance H., Sun, Ren X., de Borja, Richard, Cooper, Christopher I., Hopkins, Julia F., Govind, Shaylan K., Fung, Clement, Waggott, Daryl, Green, Jeffrey, Haider, Syed, Chan-Seng-Yue, Michelle A., Jung, Esther, Wang, Zhiyuan, Bergeron, Alain, Pra, Alan Dal, Lacombe, Louis, Collins, Colin C., Sahinalp, Cenk, Lupien, Mathieu, Fleshner, Neil E., He, Housheng H., Fradet, Yves, Tetu, Bernard, van der Kwast, Theodorus, McPherson, John D., Bristow, Robert G., and Boutros, Paul C.
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- 2017
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37. Deterministic evolution and stringent selection during pre-neoplasia
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Karlsson, Kasper, primary, Przybilla, Moritz J., additional, Kotler, Eran, additional, Khan, Aziz, additional, Xu, Hang, additional, Karagyozova, Kremena, additional, Sockell, Alexandra, additional, Wong, Wing H., additional, Liu, Katherine, additional, Mah, Amanda, additional, Lo, Yuan-Hung, additional, Lu, Bingxin, additional, Houlahan, Kathleen E., additional, Ma, Zhicheng, additional, Suarez, Carlos J., additional, Barnes, Chris P., additional, Kuo, Calvin J., additional, and Curtis, Christina, additional
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- 2022
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38. Abstract GS4-07: The Breast PreCancer Atlas DCIS genomic signatures define biology and correlate with clinical outcomes: An analysis of TBCRC 038 and RAHBT cohorts
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Strand, Siri H, primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E, additional, Seoane, Jose A, additional, King, Lorraine M, additional, Risom, Tyler, additional, Simpson, Lunden, additional, Vennam, Sujay, additional, Khan, Aziz, additional, Hardman, Timothy, additional, Harmon, Bryan E, additional, Couch, Fergus J, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla F, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Anna Maria, additional, Thompson, Alastair, additional, Gupta, Gaorav, additional, Burns, Robyn, additional, Veis, Deborah J, additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X, additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R, additional, Colditz, Graham A, additional, Hwang, E Shelley, additional, and West, Robert B, additional
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- 2022
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39. Additional file 2 of Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena
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Khoo, Amanda, Liu, Lydia Y., Sadun, Taylor Y., Salmasi, Amirali, Pooli, Aydin, Felker, Ely, Houlahan, Kathleen E., Ignatchenko, Vladimir, Raman, Steven S., Sisk, Anthony E., Reiter, Robert E., Boutros, Paul C., and Kislinger, Thomas
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body regions ,endocrine system ,fungi - Abstract
Additional file 2. Fig. S1. Tumor/NAT differences. A Consensus clustering of samples (n = 81, K = 4) using the top 25% most variable proteins (n = 1,193, K = 4). B Differentially abundant protein-coding RNAs in tumors and NATs from The Cancer Genome Atlas (TCGA). Statistically significant genes (FDR < 0.05) are colored in black. C Associations of protein abundance changes between tumor versus NAT, and mpMRI-visible NAT versus mpMRI-invisible NAT. Only proteins that were significantly differentially expressed in tumor and NAT regions (FDR < 0.05) were used for this analysis. D Associations of protein-coding RNA abundance changes between tumor versus NAT, and mpMRI-visible tumor versus mpMRI-invisible tumor. Only protein-coding RNAs that were significantly differentially expressed in tumor and NAT regions (FDR < 0.05) were used for this analysis. Proteins or transcripts that were significant (FDR < 0.05) in the tumor-NAT comparison and had the same directionality are marked in black. NAT: histologically normal prostate adjacent to the tumor; mpMRI: multiparametric magnetic resonance imaging; FDR: Benjamini-Hochberg-adjusted p-value.
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- 2022
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40. Additional file 1 of Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena
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Khoo, Amanda, Liu, Lydia Y., Sadun, Taylor Y., Salmasi, Amirali, Pooli, Aydin, Felker, Ely, Houlahan, Kathleen E., Ignatchenko, Vladimir, Raman, Steven S., Sisk, Anthony E., Reiter, Robert E., Boutros, Paul C., and Kislinger, Thomas
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Data_FILES - Abstract
Additional file 1 Methods. Method details.
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- 2022
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41. Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin
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Houlahan, Kathleen E., Prokopec, Stephenie D., Sun, Ren X., Moffat, Ivy D., Lindén, Jere, Lensu, Sanna, Okey, Allan B., Pohjanvirta, Raimo, and Boutros, Paul C.
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- 2015
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42. DCIS genomic signatures define biology and clinical outcome: Human Tumor Atlas Network (HTAN) analysis of TBCRC 038 and RAHBT cohorts
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Strand, Siri H, primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E, additional, Seoane, Jose A, additional, King, Lorraine M, additional, Risom, Tyler, additional, Simpson, Lunden A, additional, Vennam, Sujay, additional, Khan, Aziz, additional, Cisneros, Luis, additional, Hardman, Timothy, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Wei, Shi, additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla F, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Anna Maria, additional, Thompson, Alastair M, additional, Gupta, Gaorav P, additional, Burns, Robyn, additional, Veis, Deborah J, additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X, additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Anderson, Lauren, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R, additional, Colditz, Graham A, additional, Hwang, E Shelley, additional, and West, Robert B, additional
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- 2021
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43. A tumor “personality” test to guide therapeutic decision making
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Houlahan, Kathleen E., primary and Curtis, Christina, additional
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- 2021
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44. Do Breast Cancer Risk Scores Work for You?
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Houlahan, Kathleen E, primary
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- 2021
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45. Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts
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Strand, Siri H., Rivero-Gutiérrez, Belén, Houlahan, Kathleen E., Seoane, Jose A., King, Lorraine M., Risom, Tyler, Simpson, Lunden A., Vennam, Sujay, Khan, Aziz, Cisneros, Luis, Hardman, Timothy, Harmon, Bryan, Couch, Fergus, Gallagher, Kristalyn, Kilgore, Mark, We, Shi, DeMichele, Angela, King, Tari, McAuliffe, Priscilla F., Nangia, Julie, Lee, Joanna, Tseng, Jennifer, Storniolo, Anna Maria, Thompson, Alastair M., Gupta, Gaorav P., Burns, Robyn, Veis, Deborah J., DeSchryver, Katherine, Zhu, Chunfang, Matusiak, Magdalena, Wang, Jason, Zhu, Shirley X., Tappenden, Jen, Ding, Daisy Yi, Zhang, Dadong, Luo, Jingqin, Jiang, Shu, Varma, Sushama, Anderson, Lauren, Straub, Cody, Srivastava, Sucheta, Curtis, Christina, Tibshirani, Rob, Angelo, Robert Michael, Hall, Allison, Owzar, Kouros, Polyak, Kornelia, Maley, Carlo, Marks, Jeffrey R., Colditz, Graham A., Hwang, E. Shelley, and West, Robert B.
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- 2023
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46. The Human Tumor Atlas Network (HTAN) Breast Precancer Atlas: A Multi-Omic Integrative Analysis of Ductal Carcinoma in situ With Clinical Outcomes
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Strand, Siri H., primary, Rivero-Gutiérrez, Belén, additional, Houlahan, Kathleen E., additional, Seoane, Jose A., additional, King, Lorraine, additional, Risom, Tyler, additional, Simpson, Lunden A., additional, Vennam, Sujay, additional, Kahn, Aziz, additional, Cisneros, Luis, additional, Hardman, Timothy, additional, Harmon, Bryan, additional, Couch, Fergus, additional, Gallagher, Kristalyn, additional, Kilgore, Mark, additional, Rocque, Gabrielle B., additional, DeMichele, Angela, additional, King, Tari, additional, McAuliffe, Priscilla, additional, Nangia, Julie, additional, Lee, Joanna, additional, Tseng, Jennifer, additional, Storniolo, Ana Maria, additional, Thompson, Alastair, additional, Gupta, Gaorav, additional, Burns, Robyn, additional, Veis, Deborah J., additional, DeSchryver, Katherine, additional, Zhu, Chunfang, additional, Matusiak, Magdalena, additional, Wang, Jason, additional, Zhu, Shirley X., additional, Tappenden, Jen, additional, Ding, Daisy Yi, additional, Zhang, Dadong, additional, Luo, Jingqin, additional, Jiang, Shu, additional, Varma, Sushama, additional, Anderson, Lauren, additional, Straub, Cody, additional, Srivastava, Sucheta, additional, Curtis, Christina, additional, Tibshirani, Rob, additional, Angelo, Robert Michael, additional, Hall, Allison, additional, Owzar, Kouros, additional, Polyak, Kornelia, additional, Maley, Carlo, additional, Marks, Jeffrey R., additional, Colditz, Graham A., additional, Hwang, E. Shelley, additional, and West, Robert B., additional
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- 2021
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47. Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity.
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Houlahan, Kathleen E., Khan, Aziz, Greenwald, Noah F., Vivas, Cristina Sotomayor, West, Robert B., Angelo, Michael, and Curtis, Christina
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METASTATIC breast cancer , *BREAST , *HER2 positive breast cancer , *TRIPLE-negative breast cancer , *BRCA genes , *GENE amplification - Abstract
The article discusses a study on mimicking the human sense of touch conducted by Liu et al., published in the journal "Science."It mentions that by designing and fabricating an electronic skin guided by artificial intelligence, the researchers successfully replicated Merkel cells and Ruffini endings, enabling the detection of external forces and strain, with potential applications in food freshness detection through touch-sensitive measurements.
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- 2024
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48. Nursing Care of Patients with Childhood Cancer
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Branowicki, Patricia A., primary, Houlahan, Kathleen E., additional, and Conley, Susanne B., additional
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- 2009
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49. Contributors
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Albritton, Karen, primary, Amatruda, James F., additional, Anderson, Megan E., additional, Argani, Pedram, additional, Armstrong, Scott A., additional, Baker, Sharyn D., additional, Barfield, Raymond C., additional, Barr, Frederic G., additional, Berde, Charles B., additional, Berman, Jason N., additional, Bernstein, Mark L., additional, Bhatia, Smita, additional, Billett, Amy Louise, additional, Blackman, Samuel, additional, Branowicki, Patricia A., additional, Casey, Robert L., additional, Chi, Susan N., additional, Clark, Jennifer J., additional, Conley, Susanne B., additional, Davis, Ian J., additional, Degar, Barbara A., additional, DeSantes, Kenneth B., additional, Diller, Lisa, additional, Dome, Jeffrey S., additional, DuBois, Steven G., additional, Duncan, Janet, additional, Dunn, Ian F., additional, Evan, Elana E., additional, Evans, William E., additional, Felix, Carolyn A., additional, Ferrando, Adolfo A., additional, Fisher, David E., additional, Fleming, Mark D., additional, Fletcher, Jonathan A., additional, Folkman, Judah, additional, Frazier, A. Lindsay, additional, Gebhardt, Mark C., additional, George, Rani E., additional, Goldberg, John M., additional, Gorlick, Richard, additional, Grabowski, Eric F., additional, Grier, Holcombe E., additional, Haas-Kogan, Daphne, additional, Hahn, William C., additional, Herrington, Betsy, additional, Houlahan, Kathleen E., additional, Italiano, Joseph E., additional, Janeway, Katherine A., additional, Kenney, Lisa B., additional, Kieran, Mark W., additional, Kim, Heung Bae, additional, Kiss, Szilárd, additional, Kodish, Eric, additional, Koh, Andrew Y., additional, Lechpammer, Mirna, additional, Leiderman, Yannek I., additional, Lessnick, Stephen L., additional, Look, A. Thomas, additional, Mack, Jennifer W., additional, Marcus, Karen J., additional, Mukai, Shizuo, additional, Mullen, Elizabeth, additional, O'Sullivan, Maureen J., additional, Pappo, Alberto, additional, Perez-Atayde, Antonio R., additional, Pizzo, Philip A., additional, Prabhu, Sanjay P., additional, Recklitis, Christopher J., additional, Reiter, Alfred, additional, Roberts, Charles W.M., additional, Robison, Leslie L., additional, Rollins, Barrett J., additional, Samuel, David, additional, Schlis, Krysta D., additional, Segal, Rosalind A., additional, Sellers, William R., additional, Shamberger, Robert C., additional, Shusterman, Suzanne, additional, Silverman, Lewis B., additional, Sondel, Paul M., additional, Sparreboom, Alex, additional, Stegmaier, Kimberly, additional, Tomlinson, Gail E., additional, Turner, Christopher, additional, Ullrich, Christina K., additional, Voss, Stephan D., additional, Vrooman, Lynda M., additional, Weldon, Christopher B., additional, Whangbo, Jennifer, additional, Wolfe, Joanne, additional, Womer, Richard B., additional, and Zeltzer, Lonnie, additional
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- 2009
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50. Molecular hallmarks of multiparametric MRI visibility in prostate cancer
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Houlahan, Kathleen E., Salmasi, Amirali, Sadun, Taylor Y., Pooli, Aydin, Felker, Ely R., Livingstone, Julie, Huang, Vincent, Raman, Steven S., Ahuja, Preeti, Sisk, Anthony E., Boutros, Paul C., and Reiter, Robert E.
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Male ,Humans ,Prostatic Neoplasms ,Genomics ,Multiparametric Magnetic Resonance Imaging ,Neoplasm Grading ,Magnetic Resonance Imaging ,Article - Abstract
Multiparametric magnetic resonance imaging (mpMRI) has transformed management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumours are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumour. We therefore profiled the genomes and transcriptomes of 40 ISUP Grade 2 tumors: 20 mpMRI invisible (PI-RADSv2 < 3) and 20 mpMRI visible (PI-RADSv2 5). mpMRI visible tumours were enriched for hallmarks of nimbosus, an aggressive pathological, molecular and microenvironmental phenomenon in prostate cancer. These hallmarks included more genomes with more somatic mutations, increased prevalence of IDC/CA pathology and altered abundance of 102 transcripts, including overexpression of non-coding RNAs like SCHLAP1. Multiple snoRNAs were identified, and a snoRNA signature synergized with nimbosus hallmarks to discriminate visible from invisible tumours. These data suggest a confluence of aggressive molecular and microenvironmental phenomena underlie mpMRI visibility of localized prostate cancer.
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- 2019
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