Pathology, research and practice最新文献

{"title":"Targeting Wnt signaling in cancer drug resistance: Insights from pre-clinical and clinical research","authors":"Kiavash Hushmandi ,&nbsp;Mina Alimohammadi ,&nbsp;Mohammad Heiat ,&nbsp;Mehrdad Hashemi ,&nbsp;Noushin Nabavi ,&nbsp;Teimour Tabari ,&nbsp;Mehdi Raei ,&nbsp;Amir Reza Aref ,&nbsp;Najma Farahani ,&nbsp;Salman Daneshi ,&nbsp;Afshin Taheriazam","doi":"10.1016/j.prp.2025.155837","DOIUrl":"10.1016/j.prp.2025.155837","url":null,"abstract":"<div><div>Cancer drug resistance, encompassing both acquired and intrinsic chemoresistance, remains a significant challenge in the clinical management of tumors. While advancements in drug discovery and the development of various small molecules and anti-cancer compounds have improved patient responses to chemotherapy, the frequent and prolonged use of these drugs continues to pose a high risk of developing chemoresistance. Therefore, understanding the primary mechanisms underlying drug resistance is crucial. Wnt proteins, as secreted signaling molecules, play a pivotal role in transmitting signals from the cell surface to the nucleus. Aberrant expression of Wnt proteins has been observed in a variety of solid and hematological tumors, where they contribute to key processes such as proliferation, metastasis, stemness, and immune evasion, often acting in an oncogenic manner. Notably, the role of the Wnt signaling pathway in modulating chemotherapy response in human cancers has garnered significant attention. This review focuses on the involvement of Wnt signaling and its related molecular pathways in drug resistance, highlighting their associations with cancer hallmarks, stemness, and tumorigenesis linked to chemoresistance. Additionally, the overexpression of Wnt proteins has been shown to accelerate cancer drug resistance, with regulation mediated by non-coding RNAs. Elevated Wnt activity reduces cell death in cancers, particularly by affecting mechanisms like apoptosis, autophagy, and ferroptosis. Furthermore, pharmacological compounds and small molecules have demonstrated the potential to modulate Wnt signaling in cancer therapy. Given its impact, Wnt expression can also serve as a prognostic marker and a factor influencing survival outcomes in human cancers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"267 ","pages":"Article 155837"},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastasis and chemoresistance in breast cancer: Crucial function of ZEB1/2 proteins","authors":"Seyed Mohammad Doodmani ,&nbsp;Mohamad Hosein Safari ,&nbsp;Mohammadarian Akbari ,&nbsp;Najma Farahani ,&nbsp;Mina Alimohammadi ,&nbsp;Amir Reza Aref ,&nbsp;Fatemeh Tajik ,&nbsp;Amin Maghsoodlou ,&nbsp;Salman Daneshi ,&nbsp;Teimour Tabari ,&nbsp;Afshin Taheriazam ,&nbsp;Maliheh Entezari ,&nbsp;Noushin Nabavi ,&nbsp;Mehrdad Hashemi","doi":"10.1016/j.prp.2025.155838","DOIUrl":"10.1016/j.prp.2025.155838","url":null,"abstract":"<div><div>Breast cancer remains one of the leading causes of mortality worldwide. While advancements in chemotherapy, immunotherapy, radiotherapy, and targeted therapies have significantly improved breast cancer treatment, many patients are diagnosed at advanced stages, where tumor cells exhibit aggressive behavior and therapy resistance. Understanding the mechanisms driving breast cancer progression is therefore critical. Metastasis is a major factor that drastically reduces patient prognosis and survival, accounting for most breast cancer-related deaths. ZEB proteins have emerged as key regulators of cancer metastasis. Beyond their role in metastasis, ZEB proteins also influence drug resistance. This review focuses on the role of ZEB1 and ZEB2 in regulating breast cancer metastasis. These proteins interact with components of the tumor microenvironment (TME) to drive cancer progression and metastasis. Additionally, ZEB proteins regulate angiogenesis through interactions with VEGF. Targeting ZEB proteins offers potential therapeutic benefits, particularly for aggressive breast cancer subtypes such as triple-negative breast cancer (TNBC), which often show poor therapeutic response. ZEB proteins also influence the sensitivity of breast cancer cells to chemotherapy, making them promising targets for enhancing treatment efficacy. Given their upregulation in breast cancer, ZEB proteins can serve as valuable diagnostic and prognostic markers.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"267 ","pages":"Article 155838"},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of histological immunophenotype in papillary renal cell carcinoma with gene signatures related to the therapeutic effect of systemic therapy","authors":"Masanori Shiohara ,&nbsp;Chisato Ohe ,&nbsp;Nozomi Tsujio ,&nbsp;Rena Uno ,&nbsp;Kenichi Kohashi","doi":"10.1016/j.prp.2024.155764","DOIUrl":"10.1016/j.prp.2024.155764","url":null,"abstract":"<div><div>To predict the therapeutic response of systemic therapy, comprehensive analyses of the tumor microenvironment in papillary renal cell carcinoma (pRCC) have been conducted previously using immunohistochemistry and RNA sequencing. This study aimed to evaluate the correlation between hematoxylin and eosin-based histological immunophenotypes and gene signatures employed in several clinical trials predicting responsiveness to immune checkpoint inhibitors and tyrosine kinase inhibitors, using data from the Cancer Genome Atlas (TCGA)-KIRP cohort (n = 254). Herein, we evaluated tumor-associated immune cells (TAICs) using three methodologies previously reported in clear cell RCC: a 3-tier immunophenotype (desert, excluded, and inflamed) based on the spatial distribution of TAICs; a 4-tier immunophenotype (cold, immune-low, excluded, and hot) considering both the location and degree of TAICs; and an inflammation score (score 0, 1, and 2) focusing only on the degree of TAICs. Furthermore, we compared the predictive ability of the three immunophenotypes. The histological immunophenotype in pRCC exhibited a correlation with adverse clinicopathological factors (including higher stage, WHO/ISUP grade, and the presence of sarcomatoid/rhabdoid changes), gene signatures related to angiogenesis, Teff, myeloid cells, JAVELIN Renal 101 Immuno, and immune checkpoints, as well as a poorer prognosis. Among the three methodologies, the 4-tier immunophenotype demonstrated the strongest correlation with gene signatures. In conclusion, the 4-tier immunophenotype may yield potential predictive biomarkers for pRCC and guide treatment decisions.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155764"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of CacyBP/SIP expression and its relationship with ERK1/2 and p38 kinase in testicular seminoma","authors":"Grzegorz Młynarczyk ,&nbsp;Natalia Domian ,&nbsp;Alicja Lewandowska ,&nbsp;Irena Kasacka","doi":"10.1016/j.prp.2024.155750","DOIUrl":"10.1016/j.prp.2024.155750","url":null,"abstract":"<div><div>Testicular cancer accounts for approximately 5 % of all urologic cancers. The most common histopathological diagnosis of testicular neoplastic lesions are germ cell tumors (90–95 % of cases), among which the majority of cases are seminomas, the most common malignant tumors among men aged 15–44. For better clinical diagnosis and treatment, it is important to understand the molecular mechanisms of tumor formation. In this study, the expression of the CacyBP/SIP protein and ERK1/2 and p38 kinases was analyzed for the first time in seminomas and normal testicular tissues. The research was carried out using archival tissue material from 30 patients undergoing surgery due to testicular seminoma, whereas the comparative material consisted of the adjacent normal tissues. Immunohistochemistry and qRT-PCR were used to identify the expression of CacyBP/SIP, ERK1/2, and p38. A marked weakening of the immunohistochemical reaction was observed in the cancerous tissue compared to the control tissue. PCR testing of the marked proteins confirmed their lower expression in seminoma. Our findings suggest the involvement of the CacyBP/SIP protein in the ERK1/2 and p38 signalling pathways, which may be involved in the processes of testicular seminoma carcinogenesis. The results of our research provide the basis for further research in this area.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155750"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher serum cystatin C and matrix metalloproteinase 9 levels effectively predict in-stent restenosis after stent implantation for intracranial and extracranial arterial stenosis","authors":"Bin Luo,&nbsp;Yahui Xu,&nbsp;Jin Bai,&nbsp;Xinlu Yao,&nbsp;Yong Kong,&nbsp;Peifu Wang,&nbsp;Jichen Du","doi":"10.1016/j.prp.2024.155751","DOIUrl":"10.1016/j.prp.2024.155751","url":null,"abstract":"<div><h3>Objective</h3><div>This paper was performed to unravel the predictive value of serum cystatin C (Cys C) and matrix metalloproteinase 9 (MMP-9) levels before vascular stent implantation for in-stent restenosis (ISR) 6–12 months after stent implantation for intracranial and extracranial arterial stenosis.</div></div><div><h3>Methods</h3><div>One hundred and ninety-eight patients who underwent dilatation stenting for intracranial and extracranial arterial stenosis and completed Digital Subtraction Angiography or head and neck CT- Angiography review were selected for the study and were divided into ISR group (n = 33) and no ISR (NISR) group (n = 165) according to the presence or absence of ISR. Serum levels of Cys C, MMP-9, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), creatinine (Cr), homocysteine (Hcy), fibrinogen (FIB), total bilirubin (TBIL), endothelin-1 (ET-1), nitric oxide (NO), angiotensin II (Ang II), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) levels before vascular stent implantation were examined and compared between groups. ROC curves were employed for analyzing the predictive value of serum Cys C and MMP-9 alone or in combination for ISR. Pearson test was utilized for analyzing the serum Cys C and MMP-9 with vasoactive substances and inflammatory cytokines in patients in the ISR group. Logistic regression analysis was implemented to analyze the factors influencing ISR 6–12 months after stent implantation for intracranial and extracranial arterial stenosis.</div></div><div><h3>Results</h3><div>Cys C, MMP-9, LDL, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP were higher in the ISR group than in the NISR group, and TBIL was lower than in the NISR group (<em>P</em> &lt; 0.05). The AUC of the combined serum Cys C and MMP-9 (AUC = 0.900) was greater than that of Cys C (AUC = 0.685) or MMP-9 (AUC = 0.870) alone (<em>P</em> &lt; 0.05). Cys C and MMP-9 levels were positively correlated with ET-1, NO, Ang II, IL-6, TNF-α, and CRP (r &gt; 0, <em>P</em> &lt; 0.05). Increased levels of Cys C, MMP-9, LDL-C, UA, Cr, Hcy, FIB, ET-1, NO, Ang II, IL-6, TNF-α, and CRP, and diabetes were risk factors for the development of ISR (OR &gt; 1, <em>P</em> &lt; 0.05), and TBil was protective factor (OR &lt; 1, <em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Serum Cys C combined with MMP-9 levels are effective in predicting ISR.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155751"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events","authors":"Jesús Delgado-de la Mora ,&nbsp;Majd Al Assaad ,&nbsp;Selda Karaaslan ,&nbsp;Kevin Hadi ,&nbsp;Ahmed Halima ,&nbsp;Aditya Deshpande ,&nbsp;Jyothi Manohar ,&nbsp;Michael Sigouros ,&nbsp;Juan S. Medina-Martínez ,&nbsp;Michael D. Lieberman ,&nbsp;Andrea Sboner ,&nbsp;Elizabeta C. Popa ,&nbsp;José Jessurun ,&nbsp;Olivier Elemento ,&nbsp;Allyson J. Ocean ,&nbsp;Erika Hissong ,&nbsp;Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155798","DOIUrl":"10.1016/j.prp.2024.155798","url":null,"abstract":"<div><div>Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic tumor with a heterogeneous clinical course and, except for radical surgery, limited treatment options. We present a comprehensive study encompassing whole-genome and RNA sequencing of 7 tumor samples from 3 metastatic PACC patients to further delineate its genomic landscape and potential therapeutic implications. Our findings reveal distinct signatures of homologous recombination deficiency (HRD) in patients harboring pathogenic germline <em>BRCA1/2</em> and <em>FANCL</em> mutations, demonstrating favorable responses to poly (ADP-ribose) polymerase 1 (PARP) inhibitors with prolonged disease-free intervals. Additionally, we first describe structural variants in PACC, including <em>BRCA1::TRIM47</em> fusion and another variant impacting <em>FANCC</em>, both events related to HRD, and we also identify alterations in the mitogen-activated protein kinase (MAPK) pathway, including <em>RAF1</em> duplication as well as novel <em>BRAF::SORBS2</em> and <em>MAP7D2::SND1</em> gene fusions, offering potential targets for therapy. Our study underscores the importance of genome and transcriptome-wide profiling of PACC, to help guide personalized treatment strategies to improve patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155798"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-17E facilitates cell proliferation and epithelial-mesenchymal transition in A549 NSCLC cells by regulating the NF-κB pathway","authors":"Chun Li ,&nbsp;Ying Zhao ,&nbsp;Chengyuan He ,&nbsp;Xingxiang Wang ,&nbsp;Qiaotong Ren ,&nbsp;Xiaodong Gai ,&nbsp;Hefei Wang","doi":"10.1016/j.prp.2024.155792","DOIUrl":"10.1016/j.prp.2024.155792","url":null,"abstract":"<div><h3>Objective</h3><div>Interleukin-17 E (IL-17E) is a pro-inflammatory cytokine that participates in the inflammatory response and tumorigenesis. However, the function of IL-17E in non-small cell lung cancer (NSCLC) remains largely unknown.</div></div><div><h3>Methods</h3><div>The clinical value of IL-17E was determined by immunohistochemistry (IHC) in 75 cases of NSCLC tissues. Furthermore, A549 cells were added with recombinant human IL-17E (rhIL-17E) or transfected with IL-17E siRNAs to evaluate the impact on cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), as well as explore the link between IL-17E and the NF-κB pathway. Experimental techniques include CCK-8, EdU, colony formation, RT-qPCR, western blotting, flow cytometry, wound-healing, transwell and immunofluorescence assay.</div></div><div><h3>Results</h3><div>IL-17E levels was elevated in NSCLC tissues and cells, which was related to higher TNM staging, positive lymph node metastasis and decreased tumor differentiation degree. Exogenous recombinant human IL-17E (rhIL-17E) treatment promoted cell proliferation, reduced cell apoptosis, and increased the level of Bcl-2/BAX. Moreover, it enhanced cell migration, invasion, EMT and phosphorylation levels of NF-κB p65. Inversely, knocking down endogenous IL-17E in A549 cells had the opposite effect. Blocking the NF-κB pathway with BAY-117082 reduced IL-17E expression and reversed the malignant effects induced by IL-17E on A549 cells.</div></div><div><h3>Conclusion</h3><div>IL-17E facilitates NSCLC progression by promoting cell proliferation and EMT via the NF-κB pathway. IL-17E could serve as a potential strategy for NSCLC treatment.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155792"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sufentanil attenuates renal ischemia-reperfusion injury via the lncRNA KCNQ1OT1/miR-211–5p/HMGB1 axis","authors":"Meihua Lin ,&nbsp;Xi Wu ,&nbsp;Shuang Zhang","doi":"10.1016/j.prp.2024.155807","DOIUrl":"10.1016/j.prp.2024.155807","url":null,"abstract":"<div><div>Inflammation is one of the most significant pathological changes in ischemia-reperfusion injury (IRI). Sufentanil has protective effects on IRI by reducing inflammatory responses. This study aimed to investigate the protective effects and possible mechanisms of sufentanil on renal IRI (RIRI). In this study, sufentanil inhibited hypoxia/reoxygenation (H/R)-treated HK-2 proliferation and apoptosis, decreased cleaved caspase3 and increased B-cell Lymphoma 2 (Bcl-2) protein expression, inhibited reactive oxygen species (ROS) generation, and reduced inflammatory factor secretion. Moreover, sufentanil inhibited KCNQ1 overlapping transcript 1 (KCNQ1OT1) expression in H/R-treated HK-2 cells, and pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211–5p inhibitor here reversed the effects of pcDNA-KCNQ1OT1. Furthermore, miR-211–5p targets the 3′UTR of high mobility group box1 (HMGB1), and HMGB1 reversed the inhibitory effects of miR-211–5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation. Mechanistic studies revealed that sufentanil alleviated H/R-treated HK-2 cell injury was mediated by inhibiting the toll like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/ nuclear factor kappa B (NF-κB) pathway. In renal ischemia-reperfusion (I/R) rats, sufentanil inhibited KCNQ1OT1, HMGB1 and cleaved caspase3 expression, promoted miR-211–5p expression and alleviated inflammatory infiltration in renal tissues.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155807"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the diagnosis and management of endometriosis: A comprehensive review","authors":"Yingying Chen ,&nbsp;Shanza Waseem ,&nbsp;Li Luo","doi":"10.1016/j.prp.2025.155813","DOIUrl":"10.1016/j.prp.2025.155813","url":null,"abstract":"<div><div>Endometriosis is a prevalent gynecological condition characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pelvic pain and infertility. This review aims to shed light on the latest advancements in diagnosing and managing endometriosis. It offers insight into the condition's pathogenesis, clinical symptoms, diagnostic techniques, and available treatment approaches. Furthermore, the article emphasizes innovative technologies and novel therapeutic strategies that promise to enhance patient outcomes significantly. This review aspires to empower clinicians to deliver the highest quality care to their patients affected by this challenging condition by consolidating the current understanding of endometriosis.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155813"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984375","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":"Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors","authors":"Jesús Delgado-de la Mora ,&nbsp;Majd Al Assaad ,&nbsp;Stephanie Quitian ,&nbsp;Max F. Levine ,&nbsp;Aditya Deshpande ,&nbsp;Michael Sigouros ,&nbsp;Jyothi Manohar ,&nbsp;Juan S. Medina-Martínez ,&nbsp;Andrea Sboner ,&nbsp;Olivier Elemento ,&nbsp;José Jessurun ,&nbsp;Erika Hissong ,&nbsp;Juan Miguel Mosquera","doi":"10.1016/j.prp.2024.155782","DOIUrl":"10.1016/j.prp.2024.155782","url":null,"abstract":"<div><div>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs. This study sheds light on the clinical importance of alterations in cell cycle genes such as cyclin-dependent kinase 2 A (<em>CDKN2A),</em> and cyclin-dependent kinase 2B <em>(CDKN2B)</em>, their frequent alteration in metastatic GISTs and their potential role in tumor progression of this neoplasm. Likewise, new structural variations were identified in cyclin-dependent kinase 12 (<em>CDK12</em>). Whole genome profiling of metastatic GIST provides new insights to advance precision care of the disease, focusing on new therapeutic possibilities, especially for emerging targets such as <em>CDK12</em>.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"266 ","pages":"Article 155782"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}