Cancer Genomics & Proteomics最新文献

{"title":"<i>H19</i> in Serum Extracellular Vesicles Reflects Resistance to AR Axis-targeted Therapy Among CRPC Patients.","authors":"Taku Kato,&nbsp;Kyojiro Kawakami,&nbsp;Kosuke Mizutani,&nbsp;Tatsuya Ando,&nbsp;Yasuhiro Sakai,&nbsp;Kouhei Sakurai,&nbsp;Shohei Toyota,&nbsp;Hidetoshi Ehara,&nbsp;Hiroyasu Ito,&nbsp;Masafumi Ito","doi":"10.21873/cgp.20397","DOIUrl":"10.21873/cgp.20397","url":null,"abstract":"<p><strong>Background/aim: </strong>We aimed to evaluate the changes of androgen receptor (AR) signaling-related long non-coding RNAs (lncRNAs) in serum extracellular vesicles (EVs) from prostate cancer (PC) patients, in order to identify novel biomarkers for AR axis-targeted therapy (ARAT)-resistance among castration-resistant PC (CRPC) patients.</p><p><strong>Patients and methods: </strong>EVs were isolated from 2 patients before and after acquiring ARAT-resistance. RNA profiling of EVs was performed by RNA-sequencing. The expression levels of selected lncRNAs in EVs were analyzed by digital droplet PCR (ddPCR) in 58 localized and 14 metastatic PC patients at diagnosis, 7 ARAT-naïve and 6 ARAT-resistant CRPC patients. LncRNA H19 expression in PC tissue was examined using published data. In order to analyze the role of H19, the prognosis was analyzed in PC patients and proteomic analysis was performed in 22Rv1 PC cells.</p><p><strong>Results: </strong>RNA-sequencing revealed that AR-regulated RNAs were most enriched in EVs after acquiring ARAT-resistance. Among them, up-regulation of AR signaling-related lncRNAs (PCAT1, H19, HOXA-11AS, ZEB1-AS1, ARLNC1, PART1, CTBP1-AS and PCA3) was confirmed by ddPCR. H19 contained in EVs (EV-H19) was significantly increased among ARAT-resistant patients compared to ARAT-naïve CRPC or metastatic PC patients. In PC tissue, H19 was negatively correlated with AR protein and AR-activity score and up-regulated in neuroendocrine CRPC tissue with low AR expression. Furthermore, EV-H19 expression was significantly associated with worse outcome to androgen-deprivation therapy. Proteomic analysis demonstrated that H19 knockdown enhanced PC-related protein expression.</p><p><strong>Conclusion: </strong>EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464938/pdf/cgp-20-456.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide Detection of Chimeric Transcripts in Early-stage Non-small Cell Lung Cancer.","authors":"Yaroslav Ilnytskyy,&nbsp;Lars Petersen,&nbsp;John B McIntyre,&nbsp;Mie Konno,&nbsp;Adrijana D'Silva,&nbsp;Michelle Dean,&nbsp;Anifat Elegbede,&nbsp;Andrey Golubov,&nbsp;Olga Kovalchuk,&nbsp;Igor Kovalchuk,&nbsp;Gwyn Bebb","doi":"10.21873/cgp.20394","DOIUrl":"10.21873/cgp.20394","url":null,"abstract":"<p><strong>Background/aim: </strong>Lung cancer remains the main culprit in cancer-related mortality worldwide. Transcript fusions play a critical role in the initiation and progression of multiple cancers. Treatment approaches based on specific targeting of discovered driver events, such as mutations in EGFR, and fusions in NTRK, ROS1, and ALK genes led to profound improvements in clinical outcomes. The formation of chimeric proteins due to genomic rearrangements or at the post-transcriptional level is widespread and plays a critical role in tumor initiation and progression. Yet, the fusion landscape of lung cancer remains underexplored.</p><p><strong>Materials and methods: </strong>We used the JAFFA pipeline to discover transcript fusions in early-stage non-small cell lung cancer (NSCLC). The set of detected fusions was further analyzed to identify recurrent events, genes with multiple partners and fusions with high predicted oncogenic potential. Finally, we used a generalized linear model (GLM) to establish statistical associations between fusion occurrences and clinicopathological variables. RNA sequencing was used to discover and characterize transcript fusions in 270 NSCLC samples selected from the Glans-Look specimen repository. The samples were obtained during the early stages of disease prior to the initiation of chemo- or radiotherapy.</p><p><strong>Results: </strong>We identified a set of 792 fusions where 751 were novel, and 33 were recurrent. Four of the 33 recurrent fusions were significantly associated with clinicopathological variables. Several of the fusion partners were represented by well-established oncogenes ERBB4, BRAF, FGFR2, and MET.</p><p><strong>Conclusion: </strong>The data presented in this study allow researchers to identify, select, and validate promising candidates for targeted clinical interventions.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464939/pdf/cgp-20-417.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Biomarkers Related to the Efficacy of Radiotherapy in Pancreatic Cancer.","authors":"Gabriel Henrique Caxali, Laíza Brugnerotto, Mirian Carolini Esgoti Aal, Camila Ferreira Bannwart Castro, Flávia Karina Delella","doi":"10.21873/cgp.20400","DOIUrl":"10.21873/cgp.20400","url":null,"abstract":"<p><strong>Background/aim: </strong>Pancreatic cancer (PC) has one of the highest mortality rates, with an overall five-year survival rate of only 7%. When diagnosed, PC is limited to the pancreas in only 20% of patients, whereas in 50% it has already metastasized. This is due to its late diagnosis, which makes the treatments used, such as radiotherapy, difficult, and reduces survival rates. Therefore, the importance of this study in detecting genes that may become possible biomarkers for this type of tumor, especially regarding the human secretome, is highlighted. These genes participate in pathways that are responsible for tumor migration and resistance to therapies, along with other important factors.</p><p><strong>Materials and methods: </strong>To achieve these goals, the following online tools and platforms have been expanded to discover and validate these biomarkers: The Human Protein Atlas database, the Xena Browser platform, Gene Expression Omnibus, the EnrichR platform and the Kaplan-Meier Plotter platform.</p><p><strong>Results: </strong>Our study adopted a methodology that allows the identification of potential biomarkers related to the effectiveness of radiotherapy in PC. Inflammatory pathways were predominantly enriched, related to the regulation of biological processes, primarily in cytokine-derived proteins, which are responsible for tumor progression and other processes that contribute to the development of the disease.</p><p><strong>Conclusion: </strong>Radiotherapy treatment demonstrated greater efficacy when used in conjunction with other forms of therapy since it decreased the expression of essential genes involved in several inflammatory pathways linked to tumor progression.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464945/pdf/cgp-20-487.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copy Number Variations (CNVs) Account for 10.8% of Pathogenic Variants in Patients Referred for Hereditary Cancer Testing.","authors":"Konstantinos Agiannitopoulos,&nbsp;Georgia Pepe,&nbsp;Georgios N Tsaousis,&nbsp;Kevisa Potska,&nbsp;Dimitra Bouzarelou,&nbsp;Anastasia Katseli,&nbsp;Christina Ntogka,&nbsp;Angeliki Meintani,&nbsp;Nikolaos Tsoulos,&nbsp;Stylianos Giassas,&nbsp;Vassileios Venizelos,&nbsp;Christos Markopoulos,&nbsp;Rodoniki Iosifidou,&nbsp;Sofia Karageorgopoulou,&nbsp;Christos Christodoulou,&nbsp;Ioannis Natsiopoulos,&nbsp;Konstantinos Papazisis,&nbsp;Maria Vasilaki-Antonatou,&nbsp;Eleftherios Kabletsas,&nbsp;Amanta Psyrri,&nbsp;Dimitrios Ziogas,&nbsp;Efthalia Lalla,&nbsp;Anna Koumarianou,&nbsp;Kornilia Anastasakou,&nbsp;Christos Papadimitriou,&nbsp;Vahit Ozmen,&nbsp;Sualp Tansan,&nbsp;Kerim Kaban,&nbsp;Tahsin Ozatli,&nbsp;Dan Tudor Eniu,&nbsp;Angelica Chiorean,&nbsp;Alexandru Blidaru,&nbsp;Marrit Rinsma,&nbsp;Eirini Papadopoulou,&nbsp;George Nasioulas","doi":"10.21873/cgp.20396","DOIUrl":"10.21873/cgp.20396","url":null,"abstract":"<p><strong>Background/aim: </strong>Germline copy number variation (CNV) is a type of genetic variant that predisposes significantly to inherited cancers. Today, next-generation sequencing (NGS) technologies have contributed to multi gene panel analysis in clinical practice.</p><p><strong>Materials and methods: </strong>A total of 2,163 patients were screened for cancer susceptibility, using a solution-based capture method. A panel of 52 genes was used for targeted NGS. The capture-based approach enables computational analysis of CNVs from NGS data. We studied the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and of the non-commercial tool panelcn.MOPS. Additionally, we tested the performance of digital multiplex ligation-dependent probe amplification (digitalMLPA).</p><p><strong>Results: </strong>Pathogenic/likely pathogenic variants (P/LP) were identified in 464 samples (21.5%). CNV accounts for 10.8% (50/464) of pathogenic variants, referring to deletion/duplication of one or more exons of a gene. In patients with breast and ovarian cancer, CNVs accounted for 10.2% and 6.8% of pathogenic variants, respectively. In colorectal cancer patients, CNV accounted for 28.6% of pathogenic/likely pathogenic variants.</p><p><strong>Conclusion: </strong>In silico CNV detection tools provide a viable and cost-effective method to identify CNVs from NGS experiments. CNVs constitute a substantial percentage of P/LP variants, since they represent up to one of every ten P/LP findings identified by NGS multigene analysis; therefore, their evaluation is highly recommended to improve the diagnostic yield of hereditary cancer analysis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464942/pdf/cgp-20-448.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>KRTA6A</i> and <i>FA2H</i> Are Hub Genes Associated With Cgas-STING-related Immunogenic Cell Death in Lung Adenocarcinoma.","authors":"X U He,&nbsp;Yongjun Yu,&nbsp;Xiaoyang Zhang,&nbsp;Chuan Gao,&nbsp;Hongyan Wang,&nbsp;Chuang Liu","doi":"10.21873/cgp.20399","DOIUrl":"10.21873/cgp.20399","url":null,"abstract":"<p><strong>Background/aim: </strong>The immunogenic cell death (ICD) pathway plays a crucial prognostic role in lung adenocarcinoma (LUAD) therapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an upstream mechanism that drives ICD activation, but the interaction of hub genes remains unclear. The present study aimed to investigate the hub genes involved in ICD and the cGAS-STING pathway. The prognostic performance for hub genes and related Gene Ontology (GO) terms were also investigated.</p><p><strong>Materials and methods: </strong>Gene expression data of ICD induction and cGAS-STING pathway activation samples were extracted from the Gene Expression Omnibus (GEO) database, and gene expression as well as clinical data of LUAD patients who received pharmaceutical therapy were extracted from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were identified, and protein-protein interaction (PPI) analysis was used to identify hub genes. Hazard risk (HR) scores were identified using Kaplan-Meier (K-M) and COX analyses. Gene set enrichment analysis (GSEA) was performed to identify the related GO terms, and receiver operating characteristic (ROC) analysis was used to evaluate the prognosis performance of the related gene sets.</p><p><strong>Results: </strong>A total of 22 DEGs were identified in the two GEO datasets, and six hub genes were identified by PPI analysis. Keratin 6A (KRTA6A) and fatty acid 2-hydroxylase (FA2H) were selected as the hub genes after survival analysis. GSEA and ROC analysis indicated that there was no difference between the KRTA6A and FA2H gene sets on prognosis performance.</p><p><strong>Conclusion: </strong>KRTA6A and FA2H are hub genes associated with the induction of cGAS-STING-related ICD in LUAD.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464941/pdf/cgp-20-476.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10356876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CYBA</i> as a Potential Biomarker for Renal Cell Carcinoma: Evidence from an Integrated Genetic Analysis.","authors":"Chi-Fen Chang,&nbsp;Shu-Pin Huang,&nbsp;Yu-Mei Hsueh,&nbsp;Pei-Ling Chen,&nbsp;Cheng-Hsueh Lee,&nbsp;Jiun-Hung Geng,&nbsp;Chao-Yuan Huang,&nbsp;Bo-Ying Bao","doi":"10.21873/cgp.20398","DOIUrl":"10.21873/cgp.20398","url":null,"abstract":"<p><strong>Background/aim: </strong>Oxidative stress plays an important role in various pathogenic processes, and disruption in the coordinated production of NADPH oxidase (NOX)-derived reactive oxygen species has been associated with carcinogenesis. However, little is known about whether genetic variants in NOX can contribute to the development of renal cell carcinoma (RCC).</p><p><strong>Patients and methods: </strong>This study aimed to bridge this knowledge gap by analysing the association of 10 single-nucleotide polymorphisms in the phagocyte NOX genes, CYBA and CYBB, with RCC risk and tumour characteristics in 630 RCC patients and controls. Differential gene expression and patient prognosis analyses were performed using gene expression data obtained from public databases.</p><p><strong>Results: </strong>Multivariate analysis and multiple testing corrections revealed the A allele of rs7195830 in CYBA to be a significant risk allele for RCC, compared to the G allele [odds ratio (OR)=1.70, 95% confidence interval (CI)=1.27-2.26, p<0.001]. A pooled analysis of 17 renal cancer gene expression datasets revealed a higher CYBA expression in RCC than in normal tissues. Moreover, high CYBA expression was associated with advanced tumour characteristics and worse patient prognosis.</p><p><strong>Conclusion: </strong>CYBA might play an oncogenic role in RCC and serve as a predictive indicator of patient prognosis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464943/pdf/cgp-20-469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer Analysis Reveals Cancer-dependent Expression of SOX17 and Associated Clinical Outcomes.","authors":"L I Xu,&nbsp;Youhuang Bai,&nbsp;Yihang Cheng,&nbsp;Xiujie Sheng,&nbsp;Deqiang Sun","doi":"10.21873/cgp.20395","DOIUrl":"10.21873/cgp.20395","url":null,"abstract":"<p><strong>Background/aim: </strong>SRY-box containing gene 17 (SOX17) plays a pivotal role in cancer onset and progression and is considered a potential target for cancer diagnosis and treatment. However, the expression pattern of SOX17 in cancer and its clinical relevance remains unknown. Here, we explored the relationship between the expression of SOX17 and drug response by examining SOX17 expression patterns across multiple cancer types.</p><p><strong>Materials and methods: </strong>Single-cell and bulk RNA-seq analyses were used to explore the expression profile of SOX17. Analysis results were verified with qPCR and immunohistochemistry. Survival, drug response, and co-expression analyses were performed to illustrate its correlation with clinical outcomes.</p><p><strong>Results: </strong>The results revealed that abnormal expression of SOX17 is highly heterogenous across multiple cancer types, indicating that SOX17 manifests as a cancer type-dependent feature. Furthermore, the expression pattern of SOX17 is also associated with cancer prognosis in certain cancer types. Strong SOX17 expression correlates with the potency of small molecule drugs that affect PI3K/mTOR signaling. FGF18, a gene highly relevant to SOX17, is involved in the PI3K-AKT signaling pathway. Single-cell RNA-seq analysis demonstrated that SOX17 is mainly expressed in endothelial cells and barely expressed in other cells but spreads to other cell types during the development of ovarian cancer.</p><p><strong>Conclusion: </strong>Our study revealed the expression pattern of SOX17 in pan-cancer through bulk and single-cell RNA-seq analyses and determined that SOX17 is related to the diagnosis, staging, and prognosis of some tumors. These findings have clinical implications and may help identify mechanistic pathways amenable to pharmacological interventions.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464944/pdf/cgp-20-433.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methionine Restriction Increases Exosome Production and Secretion in Breast Cancer Cells.","authors":"Sachiko Inubushi,&nbsp;Tomonari Kunihisa,&nbsp;Sachiko Mizumoto,&nbsp;Shotaro Inoue,&nbsp;Mayuko Miki,&nbsp;Atsushi Suetsugu,&nbsp;Hirokazu Tanino,&nbsp;Robert M Hoffman","doi":"10.21873/cgp.20393","DOIUrl":"10.21873/cgp.20393","url":null,"abstract":"<p><strong>Background/aim: </strong>Methionine addiction is the elevated requirement for exogenous methionine for growth and survival of cancer cells, termed the Hoffman effect. Methionine-addicted cancer cells synthesize normal or excess amounts of methionine but still need an external source of methionine. Methionine restriction (MR) by either a methionine-free medium or in vivo by a low-methionine diet or by methioninase, selectively arrests cancer cells in the late S/G₂ cell cycle phase, but not normal cells. The present study focuses on the comparison of production and secretion of exosomes by cancer cells under MR and normal conditions.</p><p><strong>Materials and methods: </strong>MDA-MB-231 cells (triple-negative breast cancer), containing exosomes labeled with CD63-GFP (CD63-GFP exosomes), were visualized by fluorescence microscopy. MDA-MB-231 cells expressing exosome-specific CD63-GFP were cultured in methionine-containing (MET+) or in methionine-free (MET-) DMEM conditions. Exosomes were isolated from conditioned medium of cultured MDA-MD-231 cells by ultracentrifugation and characterized by nanoparticle tracking analysis (NTA) and Western blotting.</p><p><strong>Results: </strong>When MDA-MB-231-CD63-GFP cells were cultured under MR conditions, they arrested their growth and CD63-GFP-expressing exosomes were strongly increased in the cells. MR resulted in approximately a 2-fold increase in exosome production and secretion per cell, even though cell growth was arrested. Methionine restriction thus resulted in elevated exosome production and secretion per surviving cell.</p><p><strong>Conclusion: </strong>Exosome production and secretion in the cancer cells increased under MR, suggesting a relation between MR and exosome production and secretion.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464940/pdf/cgp-20-412.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Undifferentiated Leukemia With a Balanced t(5;10)(q35;p12) Resulting in Fusion of <i>HNRNPH1</i> With <i>MLLT10</i>.","authors":"Ioannis Panagopoulos, Kristin Andersen, Hilde Skuterud Wik, Maren Randi Tandsæther, Francesca Micci, Sverre Heim","doi":"10.21873/cgp.20387","DOIUrl":"10.21873/cgp.20387","url":null,"abstract":"<p><strong>Background/aim: </strong>Acute undifferentiated leukemia (AUL) is leukemia which does not express lineage-specific antigens. Such cases are rare, accounting for 2.7% of all acute leukemia. The reported genetic information of AULs is limited to less than 100 cases with abnormal karyotypes and a few cases carrying chimeric genes or point mutation of a gene. We herein present the genetic findings and clinical features of a case of AUL.</p><p><strong>Case report: </strong>Bone marrow cells obtained at diagnosis from a 31-year-old patient with AUL were genetically investigated. G-Banding karyotyping revealed an abnormal karyotype: 45,X,-Y,t(5;10)(q35;p12),del(12)(p13)[12]/46,XY[5]. Array comparative genomic hybridization examination confirmed the del(12)(p13) seen by G-banding but also detected additional losses from 1q, 17q, Xp, and Xq corresponding to the deletion of approximately 150 genes from these five chromosome arms. RNA sequencing detected six HNRNPH1::MLLT10 and four MLLT10::HNRNPH1 chimeric transcripts, later confirmed by reverse-transcription polymerase chain reaction together with Sanger sequencing. Fluorescence in situ hybridization analysis showed the presence of HNRNPH1::MLLT10 and MLLT10::HNRNPH1 chimeric genes.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this is the first AUL in which a balanced t(5;10)(q35;p12) leading to fusion of HNRNPH1 with MLLT10 has been detected. The relative leukemogenic importance of the chimeras and gene losses cannot be reliably assessed, but both mechanisms were probably important in the development of AUL.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320562/pdf/cgp-20-354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Pathways in Peritoneal Mesothelioma Tumorigenesis.","authors":"Ioannis Panagopoulos,&nbsp;Kristin Andersen,&nbsp;Marta Brunetti,&nbsp;Ludmila Gorunova,&nbsp;Ben Davidson,&nbsp;Marius Lund-Iversen,&nbsp;Francesca Micci,&nbsp;Sverre Heim","doi":"10.21873/cgp.20388","DOIUrl":"https://doi.org/10.21873/cgp.20388","url":null,"abstract":"<p><strong>Background/aim: </strong>Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A, pathogenetic polymorphisms in NF2, and fusion genes which often contain the promiscuous EWSR1, FUS, and ALK as partner genes. Here, we report the cytogenomic results on two peritoneal mesotheliomas.</p><p><strong>Materials and methods: </strong>Both tumors were examined using G-banding with karyotyping and array comparative genomic hybridization (aCGH). One of them was further investigated with RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing, and fluorescence in situ hybridization (FISH).</p><p><strong>Results: </strong>In the first mesothelioma, the karyotype was 25∼26,X,+5,+7,+20[cp4]/50∼52,idemx2[cp7]/46,XX[2]. aCGH detected gains of chromosomes 5, 7, and 20 with retained heterozygosity on these chromosomes. In the second tumor, the karyotype was 46,XX,inv(10)(p11q25)[7]/46,XX[3]. aCGH did not detect any gains or losses and showed heterozygosity for all chromosomes. RNA sequencing, RT-PCR/Sanger sequencing, and FISH showed that the inv(10) fused MAP3K8 from 10p11 with ABLIM1 from 10q25. The MAP3K8::ABLIM1 chimera lacked exon 9 of MAP3K8.</p><p><strong>Conclusion: </strong>Our data, together with information on previously described mesotheliomas, illustrate two pathogenetic mechanisms in peritoneal mesothelioma: One pathway is characterized by hyperhaploidy, but with retained disomies for chromosomes 5, 7, and 20; this may be particularly prevalent in biphasic mesotheliomas. The second pathway is characterized by rearrangements of MAP3K8 from which exon 9 of MAP3K8 is lost. The absence of exon 9 from oncogenetically rearranged MAP3K8 is a common theme in thyroid carcinoma, lung cancer, and spitzoid as well as other melanoma subtypes.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320557/pdf/cgp-20-363.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}