NAR Cancer最新文献_第2页

The transcriptional landscape of endogenous retroelements delineates esophageal adenocarcinoma subtypes. 内源性逆转录酶的转录结构可划分食管腺癌亚型。

NAR Cancer Pub Date : 2023-07-26 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad040

Anastasiya Kazachenka, Jane Hc Loong, Jan Attig, George R Young, Piyali Ganguli, Ginny Devonshire, Nicola Grehan, Francesca D Ciccarelli, Rebecca C Fitzgerald, George Kassiotis

{"title":"The transcriptional landscape of endogenous retroelements delineates esophageal adenocarcinoma subtypes.","authors":"Anastasiya Kazachenka, Jane Hc Loong, Jan Attig, George R Young, Piyali Ganguli, Ginny Devonshire, Nicola Grehan, Francesca D Ciccarelli, Rebecca C Fitzgerald, George Kassiotis","doi":"10.1093/narcan/zcad040","DOIUrl":"10.1093/narcan/zcad040","url":null,"abstract":"Most cancer types exhibit aberrant transcriptional activity, including derepression of retrotransposable elements (RTEs). However, the degree, specificity and potential consequences of RTE transcriptional activation may differ substantially among cancer types and subtypes. Representing one extreme of the spectrum, we characterize the transcriptional activity of RTEs in cohorts of esophageal adenocarcinoma (EAC) and its precursor Barrett's esophagus (BE) from the OCCAMS (Oesophageal Cancer Clinical and Molecular Stratification) consortium, and from TCGA (The Cancer Genome Atlas). We found exceptionally high RTE inclusion in the EAC transcriptome, driven primarily by transcription of genes incorporating intronic or adjacent RTEs, rather than by autonomous RTE transcription. Nevertheless, numerous chimeric transcripts straddling RTEs and genes, and transcripts from stand-alone RTEs, particularly KLF5- and SOX9-controlled HERVH proviruses, were overexpressed specifically in EAC. Notably, incomplete mRNA splicing and EAC-characteristic intronic RTE inclusion was mirrored by relative loss of the respective fully-spliced, functional mRNA isoforms, consistent with compromised cellular fitness. Defective RNA splicing was linked with strong transcriptional activation of a HERVH provirus on Chr Xp22.32 and defined EAC subtypes with distinct molecular features and prognosis. Our study defines distinguishable RTE transcriptional profiles of EAC, reflecting distinct underlying processes and prognosis, thus providing a framework for targeted studies.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10370457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9885004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An integrated genomic approach identifies follistatin as a target of the p63-epidermal growth factor receptor oncogenic network in head and neck squamous cell carcinoma. 综合基因组学方法确定了follistatin是头颈部鳞状细胞癌中p63-表皮生长因子受体致癌网络的靶点。

NAR Cancer Pub Date : 2023-07-24 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad038

Akinsola Oyelakin, Jennifer Sosa, Kasturi Bala Nayak, Alexandra Glathar, Christian Gluck, Isha Sethi, Maria Tsompana, Norma Nowak, Michael Buck, Rose-Anne Romano, Satrajit Sinha

{"title":"An integrated genomic approach identifies follistatin as a target of the p63-epidermal growth factor receptor oncogenic network in head and neck squamous cell carcinoma.","authors":"Akinsola Oyelakin, Jennifer Sosa, Kasturi Bala Nayak, Alexandra Glathar, Christian Gluck, Isha Sethi, Maria Tsompana, Norma Nowak, Michael Buck, Rose-Anne Romano, Satrajit Sinha","doi":"10.1093/narcan/zcad038","DOIUrl":"10.1093/narcan/zcad038","url":null,"abstract":"Although numerous putative oncogenes have been associated with the etiology of head and neck squamous cell carcinoma (HNSCC), the mechanisms by which these oncogenes and their downstream targets mediate tumor progression have not been fully elucidated. We performed an integrative analysis to identify a crucial set of targets of the oncogenic transcription factor p63 that are common across multiple transcriptomic datasets obtained from HNSCC patients, and representative cell line models. Notably, our analysis revealed FST which encodes follistatin, a secreted glycoprotein that inhibits the transforming growth factor TGFβ/activin signaling pathways, to be a direct transcriptional target of p63. In addition, we found that FST expression is also driven by epidermal growth factor receptor EGFR signaling, thus mediating a functional link between the TGF-β and EGFR pathways. We show through loss- and gain-of-function studies that FST predominantly imparts a tumor-growth and migratory phenotype in HNSCC cells. Furthermore, analysis of single-cell RNA sequencing data from HNSCC patients unveiled cancer cells as the dominant source of FST within the tumor microenvironment and exposed a correlation between the expression of FST and its regulators with immune infiltrates. We propose FST as a prognostic biomarker for patient survival and a compelling candidate mediating the broad effects of p63 on the tumor and its associated microenvironment.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10252064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterogeneity in the gene regulatory landscape of leiomyosarcoma. 白肌瘤基因调控格局的异质性。

NAR Cancer Pub Date : 2023-07-24 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad037

Tatiana Belova, Nicola Biondi, Ping-Han Hsieh, Pavlo Lutsik, Priya Chudasama, Marieke L Kuijjer

{"title":"Heterogeneity in the gene regulatory landscape of leiomyosarcoma.","authors":"Tatiana Belova, Nicola Biondi, Ping-Han Hsieh, Pavlo Lutsik, Priya Chudasama, Marieke L Kuijjer","doi":"10.1093/narcan/zcad037","DOIUrl":"10.1093/narcan/zcad037","url":null,"abstract":"Characterizing inter-tumor heterogeneity is crucial for selecting suitable cancer therapy, as the presence of diverse molecular subgroups of patients can be associated with disease outcome or response to treatment. While cancer subtypes are often characterized by differences in gene expression, the mechanisms driving these differences are generally unknown. We set out to model the regulatory mechanisms driving sarcoma heterogeneity based on patient-specific, genome-wide gene regulatory networks. We developed a new computational framework, PORCUPINE, which combines knowledge on biological pathways with permutation-based network analysis to identify pathways that exhibit significant regulatory heterogeneity across a patient population. We applied PORCUPINE to patient-specific leiomyosarcoma networks modeled on data from The Cancer Genome Atlas and validated our results in an independent dataset from the German Cancer Research Center. PORCUPINE identified 37 heterogeneously regulated pathways, including pathways representing potential targets for treatment of subgroups of leiomyosarcoma patients, such as FGFR and CTLA4 inhibitory signaling. We validated the detected regulatory heterogeneity through analysis of networks and chromatin states in leiomyosarcoma cell lines. We showed that the heterogeneity identified with PORCUPINE is not associated with methylation profiles or clinical features, thereby suggesting an independent mechanism of patient heterogeneity driven by the complex landscape of gene regulatory interactions.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effectively utilizing publicly available databases for cancer target evaluation. 有效利用公开数据库进行癌症靶点评估。

NAR Cancer Pub Date : 2023-07-14 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad035

Daniel Croft, Puja Lodhia, Sofia Lourenco, Craig MacKay

{"title":"Effectively utilizing publicly available databases for cancer target evaluation.","authors":"Daniel Croft, Puja Lodhia, Sofia Lourenco, Craig MacKay","doi":"10.1093/narcan/zcad035","DOIUrl":"10.1093/narcan/zcad035","url":null,"abstract":"The majority of compounds designed against cancer drug targets do not progress to become approved drugs, mainly due to lack of efficacy and/or unmanageable toxicity. Robust target evaluation is therefore required before progressing through the drug discovery process to reduce the high attrition rate. There are a wealth of publicly available databases that can be mined to generate data as part of a target evaluation. It can, however, be challenging to learn what databases are available, how and when they should be used, and to understand the associated limitations. Here, we have compiled and present key, freely accessible and easy-to-use databases that house informative datasets from in vitro, in vivo and clinical studies. We also highlight comprehensive target review databases that aim to bring together information from multiple sources into one-stop portals. In the post-genomics era, a key objective is to exploit the extensive cell, animal and patient characterization datasets in order to deliver precision medicine on a patient-specific basis. Effective utilization of the highlighted databases will go some way towards supporting the cancer research community achieve these aims.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10346432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell multi-gene identification of somatic mutations and gene rearrangements in cancer. 癌症体细胞突变和基因重排的单细胞多基因鉴定。

NAR Cancer Pub Date : 2023-07-10 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad034

Susan M Grimes, Heon Seok Kim, Sharmili Roy, Anuja Sathe, Carlos I Ayala, Xiangqi Bai, Alison F Almeda-Notestine, Sarah Haebe, Tanaya Shree, Ronald Levy, Billy T Lau, Hanlee P Ji

引用次数: 0

Dysfunction of ubiquitin protein ligase MYCBP2 leads to cell resilience in human breast cancers. 泛素蛋白连接酶 MYCBP2 的功能失调会导致人类乳腺癌细胞的恢复能力下降。

NAR Cancer Pub Date : 2023-07-10 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad036

Ryan A Neff, Almudena Bosch-Gutierrez, Yifei Sun, Igor Katsyv, Won-Min Song, Minghui Wang, Martin J Walsh, Bin Zhang

{"title":"Dysfunction of ubiquitin protein ligase MYCBP2 leads to cell resilience in human breast cancers.","authors":"Ryan A Neff, Almudena Bosch-Gutierrez, Yifei Sun, Igor Katsyv, Won-Min Song, Minghui Wang, Martin J Walsh, Bin Zhang","doi":"10.1093/narcan/zcad036","DOIUrl":"10.1093/narcan/zcad036","url":null,"abstract":"Breast cancer is the most common type of cancer among women worldwide, and it is estimated that 294 000 new diagnoses and 37 000 deaths will occur each year in the United States alone by 2030. Large-scale genomic studies have identified a number of genetic loci with alterations in breast cancer. However, identification of the genes that are critical for tumorgenicity still remains a challenge. Here, we perform a comprehensive functional multi-omics analysis of somatic mutations in breast cancer and identify previously unknown key regulators of breast cancer tumorgenicity. We identify dysregulation of MYCBP2, an E3 ubiquitin ligase and an upstream regulator of mTOR signaling, is accompanied with decreased disease-free survival. We validate MYCBP2 as a key target through depletion siRNA using in vitro apoptosis assays in MCF10A, MCF7 and T47D cells. We demonstrate that MYCBP2 loss is associated with resistance to apoptosis from cisplatin-induced DNA damage and cell cycle changes, and that CHEK1 inhibition can modulate MYCBP2 activity and caspase cleavage. Furthermore, we show that MYCBP2 knockdown is associated with transcriptomic responses in TSC2 and in apoptosis genes and interleukins. Therefore, we show that MYCBP2 is an important genetic target that represents a key node regulating multiple molecular pathways in breast cancer corresponding with apparent drug resistance in our study.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/fb/zcad036.PMC10331931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Replication DNA polymerases, genome instability and cancer therapies. 复制 DNA 聚合酶、基因组不稳定性和癌症疗法。

NAR Cancer Pub Date : 2023-06-28 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad033

Juliet D Strauss, Zachary F Pursell

{"title":"Replication DNA polymerases, genome instability and cancer therapies.","authors":"Juliet D Strauss, Zachary F Pursell","doi":"10.1093/narcan/zcad033","DOIUrl":"10.1093/narcan/zcad033","url":null,"abstract":"It has been over a decade since the initial identification of exonuclease domain mutations in the genes encoding the catalytic subunits of replication DNA polymerases ϵ and δ (POLE and POLD1) in tumors from highly mutated endometrial and colorectal cancers. Interest in studying POLE and POLD1 has increased significantly since then. Prior to those landmark cancer genome sequencing studies, it was well documented that mutations in replication DNA polymerases that reduced their DNA synthesis accuracy, their exonuclease activity or their interactions with other factors could lead to increased mutagenesis, DNA damage and even tumorigenesis in mice. There are several recent, well-written reviews of replication DNA polymerases. The aim of this review is to gather and review in some detail recent studies of DNA polymerases ϵ and δ as they pertain to genome instability, cancer and potential therapeutic treatments. The focus here is primarily on recent informative studies on the significance of mutations in genes encoding their catalytic subunits (POLE and POLD1), mutational signatures, mutations in associated genes, model organisms, and the utility of chemotherapy and immune checkpoint inhibition in polymerase mutant tumors.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10304742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PKM2 dictates the poised chromatin state of PFKFB3 promoter to enhance breast cancer progression. PKM2 决定了 PFKFB3 启动子的染色质状态，从而促进了乳腺癌的进展。

NAR Cancer Pub Date : 2023-06-28 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad032

Madhura R Pandkar, Adarsh Raveendran, Kajal Biswas, Srinivas Abhishek Mutnuru, Jharna Mishra, Atul Samaiya, Tyler Malys, Alexander Y Mitrophanov, Shyam K Sharan, Sanjeev Shukla

{"title":"PKM2 dictates the poised chromatin state of PFKFB3 promoter to enhance breast cancer progression.","authors":"Madhura R Pandkar, Adarsh Raveendran, Kajal Biswas, Srinivas Abhishek Mutnuru, Jharna Mishra, Atul Samaiya, Tyler Malys, Alexander Y Mitrophanov, Shyam K Sharan, Sanjeev Shukla","doi":"10.1093/narcan/zcad032","DOIUrl":"10.1093/narcan/zcad032","url":null,"abstract":"The hypoxic milieu is a critical modulator of aerobic glycolysis, yet the regulatory mechanisms between the key glycolytic enzymes in hypoxic cancer cells are largely unchartered. In particular, the M2 isoform of pyruvate kinase (PKM2), the rate-limiting enzyme of glycolysis, is known to confer adaptive advantages under hypoxia. Herein, we report that non-canonical PKM2 mediates HIF-1α and p300 enrichment at PFKFB3 hypoxia-responsive elements (HREs), causing its upregulation. Consequently, the absence of PKM2 activates an opportunistic occupancy of HIF-2α, along with acquisition of a poised state by PFKFB3 HREs-associated chromatin. This poised nature restricts HIF-2α from inducing PFKFB3 while permitting the maintenance of its basal-level expression by harboring multiple histone modifications. In addition, the clinical relevance of the study has been investigated by demonstrating that Shikonin blocks the nuclear translocation of PKM2 to suppress PFKFB3 expression. Furthermore, TNBC patient-derived organoids and MCF7 cells-derived xenograft tumors in mice exhibited substantial growth inhibition upon shikonin treatment, highlighting the vitality of targeting PKM2. Conclusively, this work provides novel insights into the contributions of PKM2 in modulating hypoxic transcriptome and a previously unreported poised epigenetic strategy exhibited by the hypoxic breast cancer cells for ensuring the maintenance of PFKFB3 expression.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f5/8c/zcad032.PMC10304768.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9738904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DICER1 platform domain missense variants inhibit miRNA biogenesis and lead to tumor susceptibility. DICER1 平台结构域错义变体抑制 miRNA 的生物发生并导致肿瘤易感性。

NAR Cancer Pub Date : 2023-06-16 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad030

Dylan Pelletier, Anne-Laure Chong, Mona Wu, Leora Witkowski, Sophie Albert, Nelly Sabbaghian, Marc R Fabian, William D Foulkes

{"title":"DICER1 platform domain missense variants inhibit miRNA biogenesis and lead to tumor susceptibility.","authors":"Dylan Pelletier, Anne-Laure Chong, Mona Wu, Leora Witkowski, Sophie Albert, Nelly Sabbaghian, Marc R Fabian, William D Foulkes","doi":"10.1093/narcan/zcad030","DOIUrl":"10.1093/narcan/zcad030","url":null,"abstract":"The endoribonuclease DICER1 plays an essential role in the microRNA (miRNA) biogenesis pathway, cleaving precursor miRNA (pre-miRNA) stem-loops to generate mature single-stranded miRNAs. Germline pathogenic variants (GPVs) in DICER1 result in DICER1 tumor predisposition syndrome (DTPS), a mainly childhood-onset tumor susceptibility disorder. Most DTPS-causing GPVs are nonsense or frameshifting, with tumor development requiring a second somatic missense hit that impairs the DICER1 RNase IIIb domain. Interestingly, germline DICER1 missense variants that cluster in the DICER1 Platform domain have been identified in some persons affected by tumors that also associate with DTPS. Here, we demonstrate that four of these Platform domain variants prevent DICER1 from producing mature miRNAs and as a result impair miRNA-mediated gene silencing. Importantly, we show that in contrast to canonical somatic missense variants that alter DICER1 cleavage activity, DICER1 proteins harboring these Platform variants fail to bind to pre-miRNA stem-loops. Taken together, this work sheds light upon a unique subset of GPVs causing DTPS and provides new insights into how alterations in the DICER1 Platform domain can impact miRNA biogenesis.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10036445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The 3D chromatin landscape of rhabdomyosarcoma. 横纹肌肉瘤的三维染色质图谱

NAR Cancer Pub Date : 2023-06-13 eCollection Date: 2023-09-01 DOI: 10.1093/narcan/zcad028

Meng Wang, Prethish Sreenivas, Benjamin D Sunkel, Long Wang, Myron Ignatius, Benjamin Z Stanton

{"title":"The 3D chromatin landscape of rhabdomyosarcoma.","authors":"Meng Wang, Prethish Sreenivas, Benjamin D Sunkel, Long Wang, Myron Ignatius, Benjamin Z Stanton","doi":"10.1093/narcan/zcad028","DOIUrl":"10.1093/narcan/zcad028","url":null,"abstract":"Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with a lack of precision therapy options for patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in representative cell lines and patient-derived xenografts (PDXs) to define chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative RMS (FN-RMS). We have generated spike-in in situ Hi-C chromatin interaction maps for the most common FP-RMS and FN-RMS cell lines and compared our data with PDX models. In our studies, we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains and unique patterns of structural variation. Our high-depth chromatin interactivity maps and comprehensive analyses provide context for gene regulatory events and reveal functional chromatin domains in RMS.","PeriodicalId":18879,"journal":{"name":"NAR Cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/35/b7/zcad028.PMC10261698.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0