Genes, Chromosomes & Cancer最新文献

{"title":"Spindle Cell Rhabdomyosarcoma of Oral Cavity With TCF12::VGLL3 Fusion, Expanding on a Recently Described Entity With Digital Spatial Profiling and Long-Term Follow Up.","authors":"Nooshin K Dashti, Debopriya Chakraborty, Madhumala K Sadanandappa, Carina A Dehner, Paul J Zhang, Joseph A Paydarfar, Laura J Tafe","doi":"10.1002/gcc.70126","DOIUrl":"10.1002/gcc.70126","url":null,"abstract":"<p><p>Recently, a distinct, bland spindle cell neoplasm with rhabdomyoblastic phenotype, and VGLL3 rearrangement has been described. These tumors have a striking predilection for the head and neck area and so far, followed an indolent course. It remains unclear whether these tumors are best classified as true rhabdomyosarcomas. There are 11 reports of such tumors with limited follow-up. Here, we report an additional case with local recurrence, long-term follow-up and spatial profiling. The tumor occurred in the right buccal mucosa/oral commissure of a 47-year-old man. On clinical examination, the mass was firm, measuring ~1.5 cm. Biopsy and subsequent wedge excision were performed. Histologically, the tumor was composed of bland, small, spindle to ovoid cells, arranged in short fascicles and vaguely storiform architecture. The tumor cells diffusely infiltrated into skeletal muscle. There was a background of inflammatory cells including small lymphocytes and histiocytes. Neoplastic cells were positive for SMA, demsin, PAX7, myogenin and MyoD1. Whole transcriptome sequencing revealed a TCF12::VGLL3 fusion. Digital spatial profiling (DSP) identified pan-AKT expression, differential expression in the MAPK pathway, and revealed that the tumor attracted a dense T-cell rich inflammatory infiltrate. The patient had a lesion in the same location 6 years prior that underwent incisional biopsy, showed intense inflammatory infiltrate, and was interpreted as benign. FISH for VGLL3 on this tissue was positive for rearrangement. No additional adjuvant treatment was given, and the patient is alive without disease, 8 months after the major resection. Long term follow-up of 6 years with only local recurrence lends further support to the notion that these neoplasms are a class of indolent/low-grade rhabdomyoblastic tumors that are biologically and clinically distinct from fully malignant spindle cell rhabdomyosarcomas.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":"e70126"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689825","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":"Myeloid Neoplasms With a t(5;12)(q31;p13) and an Associated ETV6::ACSL6 Gene Fusion Are Diagnostically Challenging and Have a Poor Prognosis","authors":"Bettina Balk,&nbsp;Marietta Truger,&nbsp;Wencke Walter,&nbsp;Alexander Schauwvlieghe,&nbsp;Johannes Lübke,&nbsp;Torsten Haferlach,&nbsp;Claudia Haferlach,&nbsp;Andreas Reiter,&nbsp;Anna Stengel","doi":"10.1002/gcc.70119","DOIUrl":"10.1002/gcc.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>ETV6</i>::<i>ACSL6</i> fusion gene resulting from the reciprocal translocation t(5;12)(q31;p13) is a rare but recurrent aberration in patients with myeloid neoplasms of variable phenotype. Cytogenetically, there is a high resemblance to the t(5;12)(q32;p13) leading to the imatinib-sensitive <i>ETV6</i>::<i>PDGFRB</i> fusion gene. Therefore, distinction of these entities by complementary molecular genetic tools is crucial, as patients with <i>ETV6</i>::<i>ACSL6</i> fusion have a poor prognosis with no response to imatinib or alternative tyrosine kinase inhibitors (TKI). We performed a comprehensive analysis of 7 patients harboring the <i>ETV6</i>::<i>ACSL6</i> fusion, using clinical and morphological characteristics, chromosome banding analysis (CBA), fluorescence in situ hybridization (FISH) and molecular genetic analyses including whole transcriptome sequencing (WTS) as well as whole genome sequencing (WGS). Patients presented with an increase in leukocytes, eosinophils and basophils. The phenotype was a chronic myeloid neoplasm in 6 patients and acute myeloid leukemia (AML) in 1 patient. The t(5;12)(q31;p13) was the sole abnormality in four out of seven cases, and the remaining 3 cases showed a complex karyotype with ≥ 3 aberrations comprising a <i>TP53</i> deletion. No recurrent molecular mutations or other fusions were identified, suggesting that <i>ETV6</i>::<i>ACSL6</i> functions as a driver event in the pathogenesis of all cases. Five out of seven patients received intensive chemotherapy, including allogeneic hematopoietic transplantation (alloHCT) in 4 patients. The median overall survival of 5 patients with available follow-up was 11 months. We conclude that the reciprocal translocation t(5;12)(q32;p13) requires a careful and step-wise diagnostic work-up to differentiate between an underlying <i>ETV6::PDGFRB</i> fusion gene with associated excellent prognosis on imatinib and an <i>ETV6::ACSL6</i> fusion gene, for which the prognosis is poor and alloHCT appears to be a promising therapeutic option.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511485","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":"Comprehensive RNA Sequencing Analysis Reveals Heterogeneous Expression of Epstein–Barr Virus Genes in Gastric Cancer","authors":"Yasuko Fujita,&nbsp;Katsuhiro Masago,&nbsp;Eiichi Sasaki,&nbsp;Shiro Fujita,&nbsp;Katsutoshi Seto,&nbsp;Hiroaki Kuroda,&nbsp;Yoshitsugu Horio,&nbsp;Hirokazu Matsushita","doi":"10.1002/gcc.70117","DOIUrl":"10.1002/gcc.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>Epstein–Barr virus-associated gastric cancer (EBVaGC) is a distinct histological and molecular subtype of gastric cancer. Histologically, it is characterized by marked lymphocytic infiltration; molecularly, it exhibits a hypermethylated phenotype. The diagnosis of surgical pathology relies on the detection of BEV-encoded RNA in situ hybridization (EBER-ISH) in tumor cells. To diagnose the histological type related to EBV is crucial, as EBVaGC is a potential target for treatment with programed cell death-1/programed cell death ligand-1 inhibitors. This study comprehensively analyzed viral and tumor gene expression in EBVaGC using RNA sequencing (RNA-seq). Six cases of EBVaGC, including one with heterogeneous EBER-ISH expression, were investigated. RNA was extracted from formalin-fixed, paraffin-embedded tissue sections and analyzed using RNA-seq. EBER-ISH-positive and negative areas from tumors with heterogeneous EBER-ISH expression were separately collected using modified manual microdissection techniques. EBV gene expression in EBVaGCs varied among the tumors. Viral gene expression was observed even in EBER-ISH-negative lesions in tumors showing heterogeneous EBER-ISH expression. Gene expression and set enrichment analyses revealed that EBVaGC was highly immunogenic, whereas EBER-ISH-negative lesions were not. However, EBVaGC tumor gene expression patterns, including EBER-ISH-negative lesions, were classified into the same cluster. Viral RNA expression in EBVaGC was heterogenous and even <i>EBER</i> expression fluctuates, suggesting that EBV infection in EBVaGC may not be detected by EBER-ISH alone.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456657","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":"TRAF7-Mutated Fibromyxoid Spindle Cell Tumor of Bone: An Osseous Case Expanding the Spectrum of TRAF7-Mutated Tumors With Over 20 Years Clinical Follow-Up","authors":"Laura M. Warmke,&nbsp;Ani Toklu,&nbsp;Spencer M. Richardson,&nbsp;Christopher D. Collier,&nbsp;L. Daniel Wurtz,&nbsp;Lauren M. Ladd,&nbsp;Roman Shrestha,&nbsp;Devin J. Conway","doi":"10.1002/gcc.70118","DOIUrl":"10.1002/gcc.70118","url":null,"abstract":"<p><i>TRAF7</i> mutations are a rare occurrence in human cancer and have recently been described in a group of mesenchymal tumors with varying clinical course. Herein, we expand the spectrum of <i>TRAF7</i>-mutated fibromyxoid spindle cell tumors by reporting the first case to arise in bone. A 60-year-old woman presented with right knee pain and was incidentally found to have a left distal femur lesion, which was first detected 20 years prior when it was favored to be benign. Recent imaging studies revealed significant interval growth with focal cortical destruction and soft tissue extension. Histologic examination showed a bland spindle cell neoplasm with fibrous to myxoid stroma. Rare mitotic figures were present; necrosis and marked cytologic atypia were absent. Immunohistochemical work-up showed that the spindle cells only demonstrated focal cytoplasmic staining with L1CAM, and whole exome sequencing identified a <i>TRAF7</i> p.Y563C missense mutation. The tumor was resected, and the patient is recovering well at 2 months with no evidence of local recurrence or distant disease. This report is the first known case of a <i>TRAF7</i>-mutated fibromyxoid spindle cell tumor of bone with the longest clinical follow-up reported to date.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432435","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":"Extrachromosomal DNA Detection and Ultrastructural Profiling in Lung and Colorectal Cancer Models","authors":"Astari Dwiranti,&nbsp;Gina Zulfa Nabila,&nbsp;Tiara Aulia Zalyanti,&nbsp;Shadira Anindieta Irdianto,&nbsp;Anom Bowolaksono","doi":"10.1002/gcc.70115","DOIUrl":"10.1002/gcc.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung and colorectal cancers are malignancies ranked as the leading cause of cancer-related mortality worldwide. Their high mortality rate is closely associated with drug resistance driven by cancer cell heterogeneity. One of the major contributors to this heterogeneity is the presence of extrachromosomal DNA (ecDNA), circular DNA fragments located outside linear chromosomes and generated through DNA damage. ecDNA is found exclusively in cancer cells, frequently carries highly amplified oncogenes, and contributes to cancer aggressiveness. To date, no study has characterized ecDNA in A549 and HT-29 cells, representative lung and colorectal cancer cell lines. This study aimed to detect and characterize ecDNA in A549 and HT-29 cells using Giemsa staining, DAPI staining, and scanning electron microscopy (SEM). Our findings revealed the presence of ecDNA, with the percentage of 15% in A549 and 10% of HT-29 cells from the total of 180 metaphase spread chromosomes. Among these, some spreads contained a single ecDNA and two ecDNA elements, either solitary or paired. The ecDNA area ranged from 0.537 μm² to 1.162 μm², with an average of 0.85 μm² in A549 cells. The fluorescence intensity of ecDNA ranged from 152.204 A.U. to 196.109 A.U., with an average of 179.847 A.U. While the ecDNA of HT-29 exhibited an average area of 0.455 μm² with an average DAPI fluorescence intensity of 102.747 A.U. SEM imaging further revealed ring-like circular structures with an area consistent with previously reported ecDNA ultrastructural characteristics. These results suggest that ecDNA is present across different cancer cell lines and may serve as a potential biomarker as well as a promising target for future cancer therapies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377129","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":"Synonymous Variants of Potential Significance Identified by a 52-Gene Clinical Sequencing Panel in Non-Small Cell Lung Cancer","authors":"Kathleen Varty,&nbsp;Leah MacLean,&nbsp;Doha Itani,&nbsp;Monowar Hossain,&nbsp;Cenk Acar,&nbsp;James Michael,&nbsp;Trisha Daigle-Maloney,&nbsp;Robert Thompson,&nbsp;Brian Johnston,&nbsp;Crispin Russell,&nbsp;Jeanette E. Boudreau,&nbsp;Daniel Gaston,&nbsp;Tony Reiman","doi":"10.1002/gcc.70111","DOIUrl":"https://doi.org/10.1002/gcc.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Next-generation sequencing (NGS) is routinely used for lung cancer genomic profiling to identify known, actionable, non-synonymous driver mutations. Recent findings suggest that synonymous variants may also be cancer drivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We analyzed genomic data and clinical outcomes for patients (<i>n</i> = 353) with non-small cell lung cancer (NSCLC) sequenced with the Oncomine Focus 52-gene NGS panel (ThermoFisher Scientific, Waltham, MA, USA) at the Saint John Regional Hospital in New Brunswick, Canada, from January 2019 to January 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KRAS was the most commonly mutated gene in this cohort from Saint John, New Brunswick, with a higher prevalence than reported in other populations. Several novel synonymous variants were identified, including in <i>ALK</i>, <i>EGFR, FGFR2</i>, <i>FGFR3</i>, <i>MYC, NF1, NRAS</i>, and <i>PIK3CA</i>, with potential effects on MAPK/ERK and PI3K/AKT signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This cohort demonstrates both expected and distinct genomic features, including novel synonymous variants in oncogenic pathways. These findings suggest regional variation in NSCLC genomics and support further study of synonymous variants in disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224464","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":"Novel FGL2::PDGFD and TGFBI::PDGFB Fusions Expand the Molecular Spectrum of Dermatofibrosarcoma Protuberans","authors":"Jeffrey M. Cloutier,&nbsp;Mohamed A. Yakoub,&nbsp;Meera Hameed,&nbsp;Silvia Cavalchini,&nbsp;Carina A. Dehner,&nbsp;Cyril Fisher,&nbsp;Khin Thway,&nbsp;Konstantinos Linos","doi":"10.1002/gcc.70110","DOIUrl":"10.1002/gcc.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive fibroblastic neoplasm characterized by recurrent <i>COL1A1::PDGFB</i> fusions that drive autocrine PDGFR-β activation. Recent sequencing studies have revealed rare DFSPs with alternative noncanonical <i>PDGFB</i> or <i>PDGFD</i> rearrangements, underscoring the genetic diversity of PDGF-ligand activation in this tumor. Here, we describe two conventional DFSPs harboring previously unreported fusions: <i>FGL2::PDGFD</i> and <i>TGFBI::PDGFB</i>. In the first case, <i>FGL2(ex1)::PDGFD(ex6)</i> replaces the PDGFD N-terminal CUB domain with the FGL2 signal peptide, a configuration predicted to generate a constitutively active, secreted PDGFD ligand. In the second case, <i>TGFBI(ex14)::PDGFB(ex3)</i> juxtaposes <i>PDGFB</i> to the highly expressed extracellular matrix gene <i>TGFBI</i>, providing an alternative promoter context for PDGFB overexpression. Both cases showed classic DFSP morphology and diffuse CD34 expression. These findings expand the molecular landscape of DFSP and illustrate convergent mechanisms of PDGFR-β activation achieved through diverse yet functionally equivalent genomic rearrangements.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226525","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":"IRF2BP2::JAK2 Defines a Novel Kinase-Activating Fusion in Pediatric T-Cell Acute Lymphoblastic Leukemia","authors":"Fatimah B. Jalud,&nbsp;Tasnia Ibnat,&nbsp;Kaitlyn Kew,&nbsp;Lauren M. Brown,&nbsp;Kimberly Dias,&nbsp;Chelsea Mayoh,&nbsp;Hansen J. Kosasih,&nbsp;Daniel Thomas,&nbsp;Loretta M. S. Lau,&nbsp;Diane Hanna,&nbsp;Bhavna Padhye,&nbsp;Charles E. de Bock,&nbsp;Paul G. Ekert,&nbsp;Teresa Sadras","doi":"10.1002/gcc.70112","DOIUrl":"https://doi.org/10.1002/gcc.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous and clinically aggressive malignancy, where outcomes remain poor for patients with early relapse or refractory disease. Although tyrosine kinase alterations represent potentially actionable lesions, understanding of their functional and therapeutic relevance in T-ALL is limited. Here, we report the first case of an <i>IRF2BP2::JAK2</i> fusion in a pediatric patient with high-risk T-ALL, identified through whole-genome and transcriptome sequencing. Using CRISPR-Cas9 genome engineering, we modeled the <i>Irf2bp2::Jak2</i> fusion in Ba/F3 cells and showed that it confers cytokine-independent growth, localizes to the cytoplasm, and drives constitutive JAK–STAT signaling. Importantly, both type I (ruxolitinib) and type II (CHZ868) JAK inhibitors potently inhibited the fusion. These findings establish <i>IRF2BP2::JAK2</i> as a novel oncogenic driver and druggable vulnerability in T-ALL and represent the first reported instance of an <i>IRF2BP2</i> fusion directly activating a non-receptor tyrosine kinase. More broadly, this work underscores the critical role of functional modeling in defining the biological and therapeutic significance of rare genomic alterations to enable the translation of precision medicine to the clinic.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224466","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":"Novel EWSR1::TEAD3 Fusion in an Adolescent With a Highly Aggressive Peritoneal Mesothelioma","authors":"Qixing Gong,&nbsp;Jia Wei,&nbsp;Sheng Xiao","doi":"10.1002/gcc.70113","DOIUrl":"https://doi.org/10.1002/gcc.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Malignant peritoneal mesothelioma (MPM) is an exceptionally rare entity in children and adolescents, exhibiting distinct clinicopathological features compared to its adult counterpart. Unlike adult cases, it typically occurs without a history of asbestos exposure or <i>BAP1</i> inactivation. Although several driver gene fusions have been documented, the primary oncogenic triggers and molecular pathways involved remain largely undefined. Herein, we present an 18-year-old male who presented with ascites and abdominal distension. Computed tomography imaging revealed diffuse thickening of the peritoneum, including the omentum and mesentery. Histopathological examination showed a neoplasm composed of a mixture of atypical epithelioid and spindled cells infiltrating the adipose tissue. Immunohistochemically, the tumor cells were positive for cytokeratin, calretinin, CK5/6, and D2-40, and negative for CK20, MOC-31, and Ber-EP4, supporting the diagnosis of a biphasic mesothelioma. Molecular genetic studies identified a novel <i>EWSR1::TEAD3</i> gene fusion. This is the first reported case of a peritoneal mesothelioma harboring this fusion.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224465","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":"PTEN Deletions Are Associated With Tumor Progression But Unrelated to Patient Prognosis in Muscle-Invasive Urothelial Bladder Carcinomas: A Large Multi-Center Validation Study on 2710 Urothelial Bladder Carcinomas","authors":"Martina Kluth,&nbsp;Henning Plage,&nbsp;Kira Furlano,&nbsp;Sebastian Hofbauer,&nbsp;Sarah Weinberger,&nbsp;Annika Fendler,&nbsp;Bernhard Ralla,&nbsp;Simon Schallenberg,&nbsp;Sefer Elezkurtaj,&nbsp;Maximilian Lennartz,&nbsp;Andreas H. Marx,&nbsp;Henrik Samtleben,&nbsp;Margit Fisch,&nbsp;Michael Rink,&nbsp;Marcin Slojewski,&nbsp;Krystian Kaczmarek,&nbsp;Thorsten Ecke,&nbsp;Nico Adamini,&nbsp;Joachim Weischenfeldt,&nbsp;Henrik Zecha,&nbsp;Ronald Simon,&nbsp;Guido Sauter,&nbsp;Thorsten Schlomm,&nbsp;David Horst,&nbsp;Sarah Minner","doi":"10.1002/gcc.70105","DOIUrl":"10.1002/gcc.70105","url":null,"abstract":"<p>The tumor suppressor gene <i>PTEN</i> plays an important role in many cancer types. Mechanism of <i>PTEN</i> inactivation includes gene mutations and deletions. In this large multi-center study, we analyzed the impact of <i>PTEN</i> deletions on tumor aggressiveness, patient prognosis, and p53 and p16 alterations, especially in muscle-invasive urothelial bladder carcinomas to expand the results from our previous study on 686 pTa to pT4 urothelial bladder carcinomas. The <i>PTEN</i> copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format. <i>PTEN</i> deletion data were compared with clinico-pathological parameters in pTa and pT2-4 carcinomas and clinical outcomes in pT2-4 carcinomas, immunohistochemical p16 and p53 expression, and <i>TP53</i> copy number status measured by FISH from previous studies. <i>PTEN</i> deletions occurred in 18.8% of 1854 analyzable carcinomas, including 17.6% heterozygous and 1.2% homozygous deleted tumors. The <i>PTEN</i> deletion rate increased markedly from pTaG2 low-grade (3.1%), to pTaG2 high-grade (4.5%) and pTaG3 (20.7%, <i>p</i> &lt; 0.0001) carcinomas, and was 23.8% in pT2-4 carcinomas (<i>p</i> &lt; 0.0001 for pTa vs. pT2-4). In pT2-4 cancers, <i>PTEN</i> deletions were unrelated to histopathological parameters of tumor aggressiveness and patient outcome. <i>PTEN</i> deletions were significantly associated with parameters of p53 alterations and p16 overexpression. It is concluded that <i>PTEN</i> deletions accumulate with grade progression in non-invasive urothelial carcinomas of the urinary bladder. The absence of a prognostic role of <i>PTEN</i> deletions in pT2-4 urothelial carcinomas is in line with our notorious inability to predict the clinical course of these tumors by only one morphological or molecular feature.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040794","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}