Genes, Chromosomes & Cancer最新文献

{"title":"Novel PDGFRB Gene Fusions in Two Cases of Infantile Myofibromatosis","authors":"Federica Boccia,&nbsp;Sabina Barresi,&nbsp;Silvia Vallese,&nbsp;Valentina Di Martino,&nbsp;Sabrina Bombaci,&nbsp;Stefania Massuras,&nbsp;Andrea Gazzin,&nbsp;Diana Carli,&nbsp;Paola Coppo,&nbsp;Rocco Roma,&nbsp;Isabella Giovannoni,&nbsp;Alessandro Mussa,&nbsp;Rita Alaggio","doi":"10.1002/gcc.70028","DOIUrl":"10.1002/gcc.70028","url":null,"abstract":"<div>\u0000 \u0000 <p>Infantile myofibromatosis (IM) comprises a wide clinical spectrum, ranging from solitary or multicentric lesions to generalized life-threatening forms. IM is mostly linked to germline or somatic heterozygous mutations in the PDGFRβ tyrosine kinase, encoded by the <i>PDGFRB</i> gene. Treatments for IM range from wait and see approach to systemic chemotherapy, according to the clinical context. Targeted therapies, such as tyrosine kinase inhibitors (TKIs) like Imatinib, show promise in treating IM lesions with <i>PDGFRB</i> gain-of-function mutations. Here, we report the first evidence of two sporadic, multifocal IM with <i>PDGFRB</i> gene fusions. RNA sequencing analysis revealed two novel fusion transcripts involving the protein kinase domain of <i>PDGFRB</i>, with <i>UBE2I</i> and <i>FN1</i> genes, respectively. Although gene fusions are frequent and potent oncogenic drivers in soft-tissue neoplasia, fusion genes involving <i>PDGFRB</i> have not previously been linked to IM. DNA-based NGS panel testing may not detect chromosomal rearrangements, such as translocations, emphasizing the critical role of comprehensive molecular profiling, including RNA sequencing, in diagnosing and managing children with IM.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhabdomyosarcoma With EWSR1::NF2 Gene Fusion: A Case Report Potentially Expanding Its Genetic Spectrum","authors":"Carla Saoud,&nbsp;Gunes Gundem,&nbsp;Dylan Domenico,&nbsp;Juan E. Arango-Ossa,&nbsp;Damon Reed,&nbsp;Max Vaynrub,&nbsp;Elli Papaemmanouil,&nbsp;Tejus A. Bale,&nbsp;Konstantinos Linos","doi":"10.1002/gcc.70025","DOIUrl":"10.1002/gcc.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, presenting with heterogeneous clinical and molecular subtypes. While gene fusions are predominantly associated with alveolar RMS, spindle cell RMS, especially congenital and intraosseous variants, are also linked to specific gene fusions. Furthermore, recently, <i>FGFR1</i> kinase-driven RMSs were published. Here, we describe a case of RMS harboring an <i>EWSR1::NF2</i> gene fusion, a deletion-driven genetic alteration that has not been previously documented in RMS or other soft tissue tumors. The patient was a 29-year-old female who presented with a lobulated ankle mass. Histologic examination revealed a malignant round cell tumor extensively infiltrating large nerve bundles. Immunohistochemical analysis demonstrated rhabdomyoblastic differentiation, consistent with rhabdomyosarcoma. While some areas showed features resembling the sclerosing and others the embryonal subtypes, the overall findings were considered unclassifiable. Targeted RNA sequencing revealed <i>EWSR1</i>(exon 9):: <i>NF2</i>(exon 7) gene fusion, which was confirmed on whole genome and targeted DNA sequencing. The latter did not yield specific diagnostic insights but revealed mutations in <i>TSC2</i> (p.T1330M), <i>ZFHX3</i> (p.A301T), and a <i>NOTCH3</i> rearrangement, all of unknown oncogenic significance. <i>MYC</i> gene amplification was detected, but there was no evidence of chromosome 8 amplification or chromosome 11p15 loss of heterozygosity. Whole genome sequencing revealed a low tumor mutation burden (2.69/Mb) and showed no other significant potentially oncogenic events. DNA methylation studies using dimensionality reduction and unsupervised clustering placed the case within the embryonal RMS subtype. Although the absence of other oncogenic driver alterations suggests that the fusion may have played a pivotal role in pathogenesis, we cannot exclude the possibility that it represents a passenger alteration rather than a true driver mutation. If the former is true, further studies will be required to determine whether this fusion represents a novel RMS subtype or a rare driver in existing subtypes of RMS.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spindle Cell Sarcoma With Novel JAZF1::NUDT5 Gene Fusion: Report of a Previously Undescribed Neoplasm","authors":"Rebecca Fliorent,&nbsp;Syed T. Hoda,&nbsp;George Jour,&nbsp;Jose G. Mantilla","doi":"10.1002/gcc.70026","DOIUrl":"10.1002/gcc.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Gene fusions involving <i>JAZF1</i> are a recurrent event in low grade endometrial stromal sarcoma, and have been more recently described in few instances of endometrial stromal sarcoma-like tumors in the genitourinary tract of men. In this article, we describe a previously unreported spindle cell sarcoma harboring an in-frame <i>JAZF1::NUDT5</i> gene fusion, arising in the chest wall of a 51-year-old man. The tumor had unique morphologic features resembling both endometrial stromal sarcoma and endometrial stromal sarcoma-like tumors, consisting of a mixture of cytologically bland and pleomorphic spindle cells with brisk mitotic activity, within an alternating myxoid and fibrous stroma. It had diffuse immunohistochemical expression of CD10, CD34 and CD56, and variable expression of androgen receptor. To our knowledge, neoplasms with these clinico-pathologic characteristics and novel gene fusion have not been previously reported in the English language literature.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Variant Analysis of Complex Karyotype Myelodysplastic Neoplasia Through Optical Genome Mapping","authors":"Andriana Valkama,&nbsp;Sandra Vorimo,&nbsp;Anna Tervasmäki,&nbsp;Hannele Räsänen,&nbsp;Eeva-Riitta Savolainen,&nbsp;Katri Pylkäs,&nbsp;Tuomo Mantere","doi":"10.1002/gcc.70024","DOIUrl":"10.1002/gcc.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Myelodysplastic neoplasia with complex karyotype (CK-MDS) poses significant clinical challenges and is associated with poor survival. Detection of structural variants (SVs) is crucial for diagnosis, prognostication, and treatment decision-making in MDS. However, the current standard-of-care (SOC) cytogenetic testing, relying on karyotyping, often yields ambiguous results in cases with CK. Here, SV detection by novel optical genome mapping (OGM) technique was explored in 15 CK-MDS cases, which collectively harbored 85 chromosomes with abnormalities reported by SOC. Additionally, OGM was utilized in the discovery of novel SVs. Altogether, OGM detected corresponding &gt; 5 Mbp alterations for 73 out of 85 SOC reported abnormalities, resulting in an 86% concordance rate. OGM provided further specification of these abnormalities, revealing that 64% of the altered chromosomes were affected by multiple SVs or chromoanagenesis. Prominently, only 5% of missing chromosomes reported by SOC were true monosomies. In addition, OGM detected alterations in chromosomes not reported as abnormal by karyotyping in 93% of cases and provided clinically relevant gene-level information, such as SVs in <i>TP53</i>, <i>MECOM</i>, <i>NUP98</i>, <i>IKZF1</i>, and <i>ETV6</i>. Analysis of novel SVs revealed two previously unreported gene-fusions (<i>SCFD1::ZNF592</i> and <i>VPS8::LRBA</i>), both confirmed by transcriptome sequencing. Furthermore, the repositioning of <i>CCDC26</i> (8q24.21) was identified as a potential cause of inappropriate gene activation in two cases, affecting <i>MECOM</i> and <i>SOX7</i>, respectively. This study shows that OGM can significantly enhance the diagnostic analysis of SVs in CK-MDS and highlights the utility of OGM identifying novel SVs in complex cancer genomes.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration","authors":"Gioia Di Stefano,&nbsp;Anja Fischer,&nbsp;Emil Chteinberg,&nbsp;Susanne Bens,&nbsp;Rabea Wagener,&nbsp;Dmitriy Abramov,&nbsp;Patrick Adam,&nbsp;Stephan H. Bernhart,&nbsp;Arndt Borkhardt,&nbsp;Birgit Burkhardt,&nbsp;Coral Del-Val,&nbsp;Michael C. Frühwald,&nbsp;Raffaella Guazzo,&nbsp;Jessica I. Hoell,&nbsp;Michael Hummel,&nbsp;Heike Horn,&nbsp;Wolfram Klapper,&nbsp;Jens Krugmann,&nbsp;Katrin S. Kurz,&nbsp;Stefano Lazzi,&nbsp;Abner Jr. Louissaint,&nbsp;Anja Mottok,&nbsp;Ilske Oschlies,&nbsp;Raffaella Santi,&nbsp;Kristian Schafernak,&nbsp;Annette M. Staiger,&nbsp;Yanming Zhang,&nbsp;Andreas Rosenwald,&nbsp;Lorenz Trümper,&nbsp;Lorenzo Leoncini,&nbsp;German Ott,&nbsp;Reiner Siebert","doi":"10.1002/gcc.70021","DOIUrl":"10.1002/gcc.70021","url":null,"abstract":"<p>Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL. We evaluated the expression profiles of 2083 miRNAs in 25 HGCBL-11q, 7 BL, 131 DLBCL, and tonsils using the HTG EdgeSeq miRNA whole transcriptome assay. Uniform manifold approximation and projection (UMAP) and differential gene expression analyses based on DESeq2 were carried out. UMAP analysis of miRNA expression did not reveal distinct groups among the studied lymphomas. However, differential gene expression investigations detected sets of overexpressed miRNAs in HGBCL-11q when compared to BL (miR-9-3p, miR-9-5p, miR-3919, miR-129-1-3p, miR-129-2-3p, miR-331-3p, miR-196b-5p, and miR-28-5p) and DLBCL (miR-3919, miR-1290, miR-4538, and miR-4791), respectively. Notably, miR-3919 showed heterogeneous but significantly higher expression (<i>p</i>-value &lt; 0.001) in HGBCL-11q than in both, BL and DLBCL. We identified a group of differentially expressed miRNAs between HGBCL-11q vs. BL and DLBCL, with miR-3919 as the most commonly and recurrently overexpressed miRNA in HGBCL-11q.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bibliometric Analysis on the Risk Factors of Cancer","authors":"Shan Chen,&nbsp;Yuanzhao Ding","doi":"10.1002/gcc.70019","DOIUrl":"10.1002/gcc.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Given the high lethality of cancer, identifying its risk factors is crucial in both epidemiology and cancer research. This study employs a novel bibliometric analysis method, which uses the tidytext package and tidy tools in R. This approach surpasses traditional tools like VOSviewer, offering more comprehensive and complex keyword data and clearer results compared to Bibliometrix. By using R, researchers can efficiently handle useful keywords, ignore irrelevant terms, adjust specific settings, and correct errors such as repeated evaluations. This study examines 1000 articles sourced from the Web of Science database, using advanced bibliometric tools like R Studio to analyze publication quantity, frequency, and word co-occurrences. The primary goal is to uncover key risk factors associated with cancer and explore the underlying mechanisms that link these factors to cancer development. Risk factors are categorized into exogenous (environmental exposures and lifestyle choices) and endogenous (genetic predispositions and hormonal imbalances). By providing a comprehensive analysis of these factors, the study aims to deepen our understanding of cancer risk. This research contributes valuable insights to the broader field of cancer research and has the potential to inform future studies and strategies for cancer prevention and treatment.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Temporal Trends and Regional Variability in BRAF and KRAS Genetic Testing in Denmark (2010–2022): Implications for Precision Medicine”","authors":"","doi":"10.1002/gcc.70020","DOIUrl":"10.1002/gcc.70020","url":null,"abstract":"<p>\u0000 <span>Frost, MG</span>, <span>Jensen, KJ</span>, <span>Jimenez-Solem, E</span>, <span>Qvortrup, C</span>, <span>Kuhlmann, TP</span>, <span>Andersen, JL</span>, <span>Høgdall, E</span>, <span>Petersen, TS</span>. <span>2024</span> <span>Temporal Trends and Regional Variability in BRAF and KRAS Genetic Testing in Denmark (2010–2022): Implications for Precision Medicine</span>. <i>Genes, Chromosomes &amp; Cancer</i> <span>63</span>(<span>4</span>):e23236. https://doi.org/10.1002/gcc.23236\u0000 </p><p>We apologize for this error.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinicopathologic and Molecular Reappraisal of Myxoinflammatory Fibroblastic Sarcoma—A Controversial and Pathologically Challenging Low-Grade Sarcoma","authors":"Takeshi Hirose,&nbsp;Hsin-Yi Chang,&nbsp;Carla Saoud,&nbsp;Robert A. Lefkowitz,&nbsp;Edward Athanasian,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.70018","DOIUrl":"10.1002/gcc.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma affecting with predilection the acral soft tissues of middle-aged adults. Clinically, MIFS is associated with a high rate of local recurrence but infrequent distant metastases. The diagnosis remains challenging due to their wide histologic spectrum and overlap with reactive, benign, and low-grade malignant lesions. Moreover, a significant limitation is that molecular confirmation is achieved in only a subset of cases, due to its broad range of genetic alterations which requires a multiplatform approach. Thus, a definitive diagnosis, especially at nonacral sites and in molecularly negative cases, remains uncertain. Our goal was to perform a detailed clinicopathologic and molecular reappraisal of MIFS managed at a single tertiary cancer center with dedicated orthopedic oncology expertise. Additionally, we examined potential outcomes correlating with specific genetic alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>A cohort of 33 patients (12 males, 21 females, median age 52 years) was selected. Tumors were tested by FISH, Archer, and/or targeted NGS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>VGLL3</i> amplification was detected in 84%, <i>BRAF</i> fusions in 33% and combined <i>TGFBR3/MGEA5</i> rearrangements in 32% of cases. Two novel fusions were detected, <i>RRAGB::CCNB3</i> and <i>FGFR1::ZBTB47</i>. Other events included a <i>YAP1::MAML2</i> fusion in two cases, one co-existing with a <i>BRAF</i> fusion. Overall, 8 (24%) patients recurred, 4 more than once, while 4 (12%) patients developed metastasis (3 locoregional, 1 pulmonary), all associated with <i>VGLL3</i> gene amplification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Positive margin status was associated with increased recurrence and reduced disease-free survival (DFS, <i>p</i> = 0.02). Moreover, it emphasizes the impact of multiplatform molecular testing in confirming the diagnosis. The lack of both local recurrence and metastatic potential outside <i>VGLL3</i> amplifications requires further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMARCA4 Deficiency in Lung Cancer: From Signaling Pathway to Potential Therapeutic Targets","authors":"Mingzhu Zhang,&nbsp;Youhong Dong,&nbsp;Rui Meng,&nbsp;Dongdong Zhang","doi":"10.1002/gcc.70022","DOIUrl":"10.1002/gcc.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>SMARCA4-deficient lung cancer, including thoracic SMARCA4-deficient undifferentiated tumors and SMARCA4-deficient nonsmall-cell lung carcinomas, is a rare and aggressive disease characterized by rapid progression and poor prognosis. This cancer was identified as a distinct entity with specific morphologic and molecular features in the 2021 WHO Classification of Thoracic Tumors. Molecular alterations in SMARCA4 are specific to this type of lung cancer. Deficiency in SMARCA4 suppresses the SWI/SNF tumor suppressor complex, driving tumor progression. Due to the lack of standardized treatment, most patients succumb to the disease within 6 months. This study provides a detailed analysis of the SMARCA4 pathway and its role in lung cancer. We analyzed potential therapeutic targets and agents to offer insights for the precise and effective treatment of SMARCA4-deficient lung cancer.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Transcriptomic and Gene Fusion Landscape of Pleomorphic Salivary Gland Adenomas","authors":"Maryam Kakay Afshari,&nbsp;Paloma Tejera Nevado,&nbsp;André Fehr,&nbsp;Junchi Huang,&nbsp;Fredrik Jäwert,&nbsp;Jonas A. Nilsson,&nbsp;Göran Stenman,&nbsp;Mattias K. Andersson","doi":"10.1002/gcc.70023","DOIUrl":"10.1002/gcc.70023","url":null,"abstract":"<p>Pleomorphic adenoma (PA) is the most common salivary gland tumor. PAs are characterized by chromosomal rearrangements of 8q12 and 12q14-15, leading to gene fusions involving the <i>PLAG1</i> and <i>HMGA2</i> oncogenes. Here, we performed the first comprehensive study of the transcriptomic and gene fusion landscape of 38 cytogenetically characterized PAs. RNA-seq identified <i>PLAG1</i> or <i>HMGA2</i> fusions in 33/38 cases (87%), of which 15 were novel fusions. Fusions were found also in tumors with normal karyotype, demonstrating that they are generated by cryptic rearrangements. <i>PLAG1</i> was mainly activated by promoter swapping and <i>HMGA2</i> by truncation of its 3′-part. RNA-seq revealed upregulation of genes involved in extracellular matrix production, WNT-signaling, and epithelial-mesenchymal transition in PA compared to normal salivary tissue. Principal component analysis identified two PA subclusters characterized by <i>PLAG1</i>- and <i>HMGA2</i>-activation, respectively, that differed in expression of genes involved in the immune system, cell adhesion, and microenvironment remodeling. Moreover, comparative analyses of PA and salivary carcinomas revealed that PA resembles myoepithelial carcinoma. Our study reveals new oncogenic gene fusions and expands our knowledge about the molecular underpinnings of PA.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}