Genes, Chromosomes & Cancer最新文献

{"title":"Discovery of Cis-Regulatory Mechanisms via Non-Coding Mutations in Acute Lymphoblastic Leukemia","authors":"Efe Aydın,&nbsp;Eleanor L. Woodward,&nbsp;Gladys Telliam Dushime,&nbsp;Rebeqa Gunnarsson,&nbsp;Henrik Lilljebjörn,&nbsp;Larissa H. Moura-Castro,&nbsp;Thoas Fioretos,&nbsp;Bertil Johansson,&nbsp;Kajsa Paulsson,&nbsp;Minjun Yang","doi":"10.1002/gcc.70045","DOIUrl":"https://doi.org/10.1002/gcc.70045","url":null,"abstract":"<p>The non-coding genome, constituting 98% of human DNA, remains largely unexplored, yet holds potential for identifying new biomarkers and therapeutic targets in acute lymphoblastic leukemia (ALL). In this study, we conducted a systematic analysis of recurrent somatic non-coding single nucleotide variants (SNVs) in pediatric B-cell precursor (BCP) ALL. We leveraged whole genome sequencing (WGS) data from 345 pediatric BCP ALL cases, representing all major genetic subtypes and identified 346 mutational hotspots that harbored somatic SNVs in at least three cases. Through the integration of paired RNA sequencing along with published ChIP-seq and ATAC-seq data, we found 128 non-coding hotspots associated with differentially expressed genes nearby, which were enriched for cis-regulatory elements, demonstrating the effectiveness of multi-omics integration in distinguishing pathogenic mutations from passengers. We identified one mutational hotspot that was associated with increased expression of the leukemia-associated gene <i>NRAS</i> in three primary ALLs. Micro-C analysis in the leukemia cell line demonstrated interactions between the hotspot region and <i>NRAS</i> regulatory elements. Dual luciferase assays indicated that the mutations disrupted regulatory interactions and CRISPR-mediated deletion of the region significantly upregulated <i>NRAS</i>, confirming the hypothesized regulatory link. Altogether, we provide new insights into the functional roles of non-coding mutations in leukemia.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707702","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":"Genome-Wide DNA Methylation and Copy Number Alterations in Gastrointestinal Stromal Tumors","authors":"Tony G. Kleijn,&nbsp;Baptiste Ameline,&nbsp;Roos F. Bleckman,&nbsp;Wierd Kooistra,&nbsp;Evert van den Broek,&nbsp;Gilles F. H. Diercks,&nbsp;Bettien M. van Hemel,&nbsp;Bert Timmer,&nbsp;Wim Timens,&nbsp;Gursah Kats-Ugurlu,&nbsp;Léon C. van Kempen,&nbsp;Boudewijn van Etten,&nbsp;Ed Schuuring,&nbsp;Albert J. H. Suurmeijer,&nbsp;Jacco J. de Haan,&nbsp;Daniel Baumhoer,&nbsp;Anna K. L. Reyners,&nbsp;Arjen H. G. Cleven","doi":"10.1002/gcc.70046","DOIUrl":"https://doi.org/10.1002/gcc.70046","url":null,"abstract":"<p>Gastrointestinal stromal tumors (GISTs) span a broad clinical spectrum, from indolent neoplasms to life-threatening metastatic tumors. A persistent limitation of current risk stratification systems is that a subset of GISTs is graded as low-risk but nevertheless metastasizes. Therefore, new predictive factors that improve risk stratification are needed. In this exploratory study, we investigated the potential of genome-wide DNA methylation profiling and copy number variation (CNV) analysis as additional prognostic tools for GISTs. We collected a cohort of 28 patients with GIST diagnosed between 2001 and 2022, with available follow-up and molecular data. This included 15 patients without progressive disease (seven low-risk and eight moderate- to high-risk GISTs) and 13 with progressive disease. Among those with progression, eight experienced recurrence or metastasis post-surgery (one low-risk, seven high-risk GISTs), while five had metastatic disease at initial diagnosis. Risk stratification was determined according to Miettinen's criteria. Genome-wide DNA methylation data and CNV plots were generated from imatinib-naïve primary GISTs using the Illumina Infinium MethylationEPIC BeadChip array. Unsupervised cluster analysis revealed distinct DNA methylation patterns predominantly associated with anatomical location and genotype. Differential DNA methylation analysis comparing primary gastric GISTs associated with and without progressive disease showed 8 differentially methylated regions spanning the coding and promoter areas of 6 genes. CNV analysis demonstrated that GISTs associated with progressive disease had the most CNVs, whereas low-risk, non-progressive GISTs had the fewest. Despite the limited sample size, this exploratory study indicates that genome-wide DNA methylation profiling and CNV analysis could enhance GIST risk stratification.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707703","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":"Germline Whole-Exome Sequencing in Non-Smoker Lung Cancer Patients Reveals Pathogenic Variants in Lung Cancer Driver Genes","authors":"Giovanni Carapezza,&nbsp;Simone Paolo Minardi,&nbsp;Sara Noci,&nbsp;Giulia Pintarelli,&nbsp;Susanna Zanutto,&nbsp;Matteo Incarbone,&nbsp;Davide Tosi,&nbsp;Tommaso Antonio Dragani,&nbsp;Francesca Colombo,&nbsp;Marco Alessandro Pierotti,&nbsp;Manuela Gariboldi","doi":"10.1002/gcc.70040","DOIUrl":"10.1002/gcc.70040","url":null,"abstract":"<p>Approximately 10%–15% of all lung cancers arise in non-smokers. Although there are no established aetiological factors, non-smokers with a family history of cancer have an increased risk of lung cancer, implying host genetic factors in lung cancer susceptibility. We sought to identify, in a cohort of 75 patients recruited before lung lobectomy, germline alterations with a strong association with lung cancer. Whole-exome sequencing was performed on genomic DNA from peripheral blood. Six resources were used to select pathogenic germline variants with strong clinical significance. In total, 33 pathogenic or likely pathogenic variants in 31 genes were identified. Of these, 13 were located in cancer-predisposing genes (nine were lung cancer drivers), most of which were involved in DNA repair mechanisms and diseases of metabolism. Among DNA repair-related genes, <i>BRCA1</i> and <i>BRCA2</i>, and <i>ATM</i> have also been identified in other studies on non-smokers. Our results strongly support the hypothesis that a number of non-smoker lung cancer patients carry germline variants in cancer-predisposing genes, suggesting that lung cancer patients, particularly non-smokers, should be considered for germline molecular testing.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676889","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":"SSX and SS18-SSX Antibodies as Additional Tools for Diagnosing Undifferentiated Neoplasms With the EWSR1::SSX3 Fusion","authors":"Isidro Machado,&nbsp;Antonio Llombart-Bosch,&nbsp;Caterina Fumagalli,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.70044","DOIUrl":"10.1002/gcc.70044","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676858","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":"Chromatin Interaction and Histone Mark Signatures Associated With TBXT Expression in Metastatic Lung Cancer","authors":"Reuben M. Yaa,&nbsp;Brian M. Schilder,&nbsp;Rafael D. Acemel,&nbsp;Fiona C. Wardle","doi":"10.1002/gcc.70041","DOIUrl":"https://doi.org/10.1002/gcc.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>TBXT,</i> a member of the T-box transcription factor family, drives epithelial-to-mesenchymal transition in the metastasis of some cancers. However, the relationship between the epigenetic regulatory landscape and its expression in lung cancers remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Circularized chromosome capture combined with sequencing (4C-seq) was employed to analyze physical chromatin interactions at the <i>TBXT</i> loci in the lung cancer cell line H460, a high <i>TBXT-expressing</i> cell line, compared to H358 and A549, which do not express <i>TBXT</i>. To define the regulatory landscape, the targeted <i>TBXT</i> chromatin interactions were integrated with histone modification profiles from respective cells, followed with motif analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our analysis identified distinct patterns of potential <i>cis</i>-regulatory elements (pCREs) associated with the <i>TBXT</i> promoter, with increased near-<i>cis</i> pCRE enrichment in the <i>TBXT-expressing</i> cells. Integration of pCREs with epigenetic histone modification revealed two unique pCREs in <i>TBXT-expressing</i> H460 cells enriched with the active histone mark H3K27ac, harboring binding sites for transcription factors of the forkhead box, zinc finger, and musculoaponeurotic fibrosarcoma families that are linked to cancer metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings shed light on active chromatin interactions with <i>TBXT</i> expression in lung cancers, pointing to specific DNA elements and regulatory proteins that may be involved. This knowledge paves the way for understanding <i>TBXT</i> expression dynamics at the onset and progression of metastatic cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639316","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":"EWSR1::CREM Fusion in a Pediatric Patient With Testicular Leydig Cell Tumor","authors":"Megan M. Lilley,&nbsp;Patrick R. Blackburn,&nbsp;Larissa V. Furtado,&nbsp;Alberto S. Pappo,&nbsp;Selene C. Koo","doi":"10.1002/gcc.70038","DOIUrl":"https://doi.org/10.1002/gcc.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>Sex cord-stromal tumors are rare in pediatric patients. Leydig cell tumors are a rare subset of sex cord-stromal tumors characterized by unique molecular alterations, including <i>TERT</i> fusions and mutations of <i>CTNNB1</i>, <i>FOXO4</i>, <i>TP53, NBN, MTOR, BAP1, MEN1,</i> and <i>CREBBP</i>. We report a case of a testicular Leydig cell tumor with an <i>EWSR1::CREM</i> fusion, which to our knowledge has not been previously reported in this setting.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595405","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":"FIP1L1::PDGFRA Fusion in a Pediatric Patient Presenting With B-Cell Lymphoblastic Leukemia","authors":"Jenna Nunn,&nbsp;Bronwyn Williams,&nbsp;David Deambrosis","doi":"10.1002/gcc.70037","DOIUrl":"https://doi.org/10.1002/gcc.70037","url":null,"abstract":"<p>Approximately 10% of Ph-Like patients have <i>ABL</i> class gene fusions, which include the <i>FIP1L1::PDGFRA</i> rearrangement. We report a case of a pediatric patient with Ph-like B-lymphoblastic leukemia (B-LL) with a <i>FIP1L1::PDGFRA</i> fusion and their treatment course using a combination of chemotherapy and targeted therapy with imatinib. A 10-year-old female presented with lethargy, palpitations, and fevers. She had pancytopenia, no eosinophilia, and flow cytometry consistent with B-LL. FISH identified a <i>CHIC2</i> deletion, suggestive of <i>FIP1L1::PDGFRA</i> fusion, confirmed on next-generation RNA sequencing. The patient commenced targeted therapy with imatinib, which she continued until completion of standard chemotherapy per COG AALL1732. She remains in remission 6 months post-completion of therapy. B-ALL with a <i>FIP1L1::PDGFRA</i> fusion is extremely rare, particularly in pediatrics. <i>FIP1L1::PDGFRA</i> rearrangements can be difficult to detect on routine testing and may not always be seen in association with eosinophilia. Identification of <i>FIP1L1::PDGFRA</i> rearrangements is important as they enable treatment with a tyrosine kinase inhibitor, which has significantly improved the overall prognosis for <i>PDGFRA</i>-rearranged neoplasms. Prospective studies assessing imatinib dosage, duration, and long-term safety are warranted in this cohort.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481594","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":"Schwann Cells Deficient in Neurofibromin Lack Sensitivity to Their Biomechanical Microenvironment","authors":"Micah Rambo,&nbsp;Isheka Agarwala,&nbsp;Camdyn Vanek,&nbsp;Yuxin Xiao,&nbsp;Emma Brown,&nbsp;K. L. Mills","doi":"10.1002/gcc.70036","DOIUrl":"https://doi.org/10.1002/gcc.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Plexiform neurofibromas (PNFs) are benign tumors of the peripheral nervous system that affect approximately 30% of people with neurofibromatosis type 1 (NF1). Schwann cells (SCs), the tumor progenitor cells, respond to and use biomechanical signals like tissue stiffness and mechanical loads in their maintenance and repair functions in healthy tissues. PNFs are described as having altered biomechanics, and we hypothesize this plays a role in PNF development. As a first step in studying the role that altered biomechanics may play in the development of PNFs, we aimed to determine how PNF SCs alter in their response to various biomechanical signals as compared to healthy SCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the behavior of healthy and PNF SCs in three different tissue-mimicking biomechanical models. First, we examined their spreading behavior on extracellular matrix (ECM) protein-coated polyacrylamide hydrogels of varying stiffness in the healthy and pathological range. Second, we investigated their collective migration with respect to substrate stiffness and ECM protein-coating. Finally, we generated multicellular spheroid tissue models using healthy and PNF SCs and measured their mechanical properties as a function of spheroid size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that PNF SCs are differently sensitive to substrate stiffness in a physiological range compared to healthy SCs, lack sensitivity to ECM protein coating when collectively migrating, and lack sensitivity to environmental deficiencies in oxygen and nutrient supplies when in spheroid culture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We propose that PNF SC altered biomechanics likely play a role in tumor initiation and progression, and that further biomechanical-based investigations of NF1 tumor growth are needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481593","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":"Pregnancy and the Risk for Cancer in Neurofibromatosis 1","authors":"Roope A. Kallionpää,&nbsp;Juha Määttänen,&nbsp;Jussi Leppävirta,&nbsp;Sirkku Peltonen,&nbsp;Juha Peltonen","doi":"10.1002/gcc.70017","DOIUrl":"https://doi.org/10.1002/gcc.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurofibromatosis type 1 (NF1) is associated with a high risk for cancer. Benign cutaneous neurofibromas of women with NF1 may increase in size and number during pregnancy. However, it is not known whether pregnancy affects the risk for cancer in NF1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved the pregnancies of women in the Finnish NF1 cohort and in a 10-fold control cohort from the Finnish Medical Birth Register. Cancers occurring during or after pregnancy were obtained from the Finnish Cancer Registry and summarized using standardized incidence ratio (SIR). The cancer incidence of nonNF1 mothers of individuals with NF1 was also estimated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Totals of 263 pregnancies in 136 women with NF1 and 3176 pregnancies in 1720 controls were observed. In the NF1 group, two cancers were identified during pregnancy and the year following the delivery (SIR 6.44, 95% CI 1.07–19.89). Among controls, the SIR was markedly lower (0.25, 95% CI 0.01–1.08). Within 1–10 years after pregnancy, the SIR of women with NF1 was 7.54 (95% CI 4.15–12.41). The SIR of women with NF1 aged 20–49 years, and without a known history of deliveries was 8.63 (95% CI 6.08–11.81). The nonNF1 mothers displayed a SIR of 0.81 (95% CI 0.66–1.00) after giving birth to a child with NF1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The pregnancy-related cancer incidence in women with NF1 is similar to women with NF1 aged 20–49 years overall, although notably higher than in the general population. Giving birth to a child with NF1 does not affect the risk for cancer in women without NF1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466067","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 MAZ::NCOA2 Subcutaneous Small Round Cell Sarcoma of Infancy With Diffuse S100/SOX10 Positivity: A Novel Entity","authors":"Huiyao Chen,&nbsp;Pu Zhang,&nbsp;Lingli Zhou","doi":"10.1002/gcc.70034","DOIUrl":"https://doi.org/10.1002/gcc.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Small round cell sarcomas (SRCSs) constitute a heterogeneous group of high-grade tumors with a poor prognosis, predominantly affecting children and young adults. According to the 2020 WHO Soft Tissue Tumor classification, SRCSs are categorized into Ewing sarcoma, round cell sarcoma with <i>EWSR1</i>-non-ETS fusions, <i>CIC</i>-rearranged sarcoma, and sarcoma with <i>BCOR</i> genetic alterations. Herein, we report a case of a 10-month-old boy presenting with a progressively enlarging left lumbar mass. Histopathological examination revealed a well-demarcated lesion composed of small, round to oval cells with scant cytoplasm and mildly irregular nuclei. Immunohistochemical staining demonstrated strong, diffuse positivity for S100 and SOX10, indicating neurocristic differentiation. Next-generation sequencing identified an in-frame fusion between <i>MAZ</i> exon 3 on chromosome 16 and <i>NCOA2</i> exon 12 on chromosome 8. Fluorescence in situ hybridization (FISH) confirmed a break-apart signal at the <i>NCOA2</i> locus. To the best of our knowledge, this represents the first documented instance of an <i>NCOA2</i> rearrangement involving <i>MAZ</i> in SRCSs. This case broadens the molecular spectrum of SRCSs, highlights the importance of incorporating molecular techniques into diagnostic workflows, and may have implications for future diagnostic and therapeutic strategies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466068","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}