Genes, Chromosomes & Cancer最新文献

{"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}

{"title":"PDGFRA::USP8 Fusion in a Cutaneous Inflammatory Myofibroblastic Tumor, Highlighting Genetic Pleiotropy of Kinase Gene Fusions in Soft Tissue Neoplasms","authors":"Astrid I. P. Vernemmen,&nbsp;Léon C. L. T. van Kempen,&nbsp;Frits Aarts,&nbsp;Axel zur Hausen,&nbsp;Raf M. E. Sciot,&nbsp;Jason L. Hornick,&nbsp;Mari F. C. M. van den Hout","doi":"10.1002/gcc.70035","DOIUrl":"https://doi.org/10.1002/gcc.70035","url":null,"abstract":"<p><i>PDGFRA::USP8</i> fusions have recently been described in neoplasms in the provisional category of calcified chondroid mesenchymal neoplasm (CCMN). Here, we describe a cutaneous inflammatory myofibroblastic tumor (IMT) on the upper leg of a 24-year-old male harboring the same fusion product. The tumor showed a morphology typical of IMT, including a concomitant inflammatory infiltrate; in addition, there was strong immunohistochemical PDGFRα overexpression. Methylation profiling (Sarcoma classifier v12.2) was consistent with IMT (calibrated score 0.99). Herein, we review other soft tissue tumors with <i>PDGFRA</i> fusions, emphasizing <i>PDGFRA::USP8</i> fusions, further highlighting the genetic pleiotropy of kinase gene fusions in soft tissue tumors. In addition, this case expands the landscape of kinase fusions in IMT, presented by an extremely rare cutaneous IMT.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404576","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 Novel ACVR2A::RAF1 Fusion in Spindle Cell Sarcoma","authors":"Anfeng Jiang,&nbsp;Huan Li,&nbsp;Dongbing Li,&nbsp;Huafei Chen,&nbsp;Lina Zhao,&nbsp;Ying Zhang,&nbsp;Yangyang Li,&nbsp;Rong Rong,&nbsp;Bin Li,&nbsp;Sheng Xiao","doi":"10.1002/gcc.70033","DOIUrl":"https://doi.org/10.1002/gcc.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Kinase-rearranged spindle cell sarcomas are characterized by unique molecular features. The advent of next-generation sequencing (NGS) has enabled the detection of a multitude of kinase fusions, thereby contributing to the accurate categorization of these tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 37-year-old woman experienced the fourth recurrence of a cranial base tumor 25 years following the initial surgery and radiation therapy. Histological analysis disclosed spindle-shaped and oval tumor cells, along with a high number of mitotic figures. Immunohistochemistry showed a null immunophenotype, negative for pan-TRK, S-100, CD34, pan-CK, GFAP, and Olig2. Molecular analysis of the tumor tissue identified a novel ACVR2A::RAF1 fusion, comprising the first four exons of ACVR2A and the last nine exons of RAF1. The resulting fusion protein retains the extracellular and transmembrane domains of ACVR2A, while its kinase domain is replaced by the kinase domain of RAF1. This hybrid protein likely contributes to tumorigenesis by activating RAF1 signaling in response to ACVR2A ligands from the TGF-β superfamily.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Treatment and Outcome</h3>\u0000 \u0000 <p>The patient was treated with the MEK1 inhibitor Trametinib, 2 mg per time and once a day. One month later, MRI showed significant tumor shrinkage and pain relief.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The ACVR2A::RAF1 fusion represents a novel genomic profile in RAF1-rearranged spindle cell sarcoma, offering a rational basis for targeted therapy. This case highlights the importance of molecular diagnostics in identifying actionable targets and guiding treatment, potentially leading to significant clinical benefits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404577","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":"Challenging Conventional Perceptions of Oncogenes and Tumor Suppressor Genes: A Comprehensive Analysis of Gene Expression Patterns in Cancer","authors":"Mingyuan Zou,&nbsp;Li Qiu,&nbsp;Wentao Wu,&nbsp;Hui Liu,&nbsp;Han Xiao,&nbsp;Jun Liu","doi":"10.1002/gcc.70030","DOIUrl":"https://doi.org/10.1002/gcc.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Identifying genes involved in cancer is crucial for understanding the underlying molecular mechanisms of the disease and developing effective treatment strategies. Differential expression analysis (DEA) is the predominant method used to identify cancer-related genes. This approach involves comparing gene expression levels between different samples, such as cancerous and non-cancerous tissues, to identify genes that are significantly upregulated or downregulated in cancer. DEA is based on the commonly believed assumption that genes upregulated in cancerous tissues have the potential to function as oncogenes. Their expression levels often correlate with cancer advancement and unfavorable prognosis, whereas downregulated genes display the opposite correlation. However, contrary to the prevailing belief, our analysis utilizing The Cancer Genome Atlas (TCGA) databases revealed that the upregulated or downregulated genes in cancer do not always align with cancer progression or prognosis. These findings emphasize the need for alternative approaches for identifying cancer-related genes that may be more accurate and effective. To address this need, we compared the effectiveness of machine learning (ML) methods with that of traditional DEA in the identification of cancer-related genes. ML algorithms have the advantage of being able to analyze large-scale genomic data and identify complex patterns that may go unnoticed by traditional methods. Our results demonstrated that ML methods significantly outperformed DEA in the screening of cancer-related genes.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389279","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":"Profiling Precursor microRNAs of Breast Cancer From Total RNA Sequencing Data to Gain Insights Into Their Roles and Prognostic Values","authors":"Sen Wu,&nbsp;Jia-Wern Pan,&nbsp;Marimuthu Citartan,&nbsp;Thean-Hock Tang,&nbsp;MyBrCa Collaborative Group,&nbsp;Soo-Hwang Teo,&nbsp;Ewe Seng Ch'ng","doi":"10.1002/gcc.70027","DOIUrl":"https://doi.org/10.1002/gcc.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer, a molecularly heterogeneous disease, is classified into hormone receptor-positive luminal breast cancer (LBC), human epidermal growth factor receptor 2-positive breast cancer, and triple-negative breast cancer (TNBC). Precursor microRNAs (pre-miRNAs), typically form hairpin structures with a length from 65 to 80 bases, are shown to play crucial roles in breast cancer carcinogenesis. We hypothesized that these pre-miRNAs could have been sequenced in total RNA sequencing (RNA-seq) and developed a novel algorithm to profile pre-miRNAs from raw total RNA-seq data. A total of 907 breast cancer samples curated by Malaysian Breast Cancer Genetic Study (MyBrCa) were profiled using this algorithm and a comparison was made between pre-miRNA profiles and mature miRNA profiles obtained from The Cancer Genome Atlas (TCGA) dataset. We explored differentially expressed pre-miRNAs in TNBC in comparison to LBC and conducted downstream functional analyses of the target genes. A prognostic signature was built by LASSO–Cox regression on selected pre-miRNAs and validated internally and externally by MyBrCa and TCGA datasets, respectively. As a result, 10 common differentially expressed pre-miRNAs were identified. Functional analyses of these pre-miRNAs captured certain aggressive TNBC behaviors. Importantly, a pre-miRNA signature composed of 4 out of these 10 pre-miRNAs significantly prognosticated the breast cancer patients in the MyBrCa cohort and TCGA cohort, independent of conventional prognostic factors. In conclusion, this novel algorithm allows profiling pre-miRNAs from raw total RNA-seq data, which could be cross-validated with mature miRNA profiles for cross-platform comparison. The findings of this study underscore the importance of pre-miRNAs in breast cancer carcinogenesis and as prognostic factors.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389278","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":"Influence of Cytogenetics on the Outcome of Patients With High-Risk Myelodysplastic Syndrome Including Deletion 5q Treated With Azacitidine With or Without Lenalidomide","authors":"Bengt Rasmussen,&nbsp;Lars Nilsson,&nbsp;Magnus Tobiasson,&nbsp;Martin Jädersten,&nbsp;Hege Garelius,&nbsp;Ingunn Dybedal,&nbsp;Kirsten Grønbaek,&nbsp;Elisabeth Ejerblad,&nbsp;Fryderyk Lorenz,&nbsp;Max Flogegård,&nbsp;Claus Werenberg Marcher,&nbsp;Lucia Cavalier,&nbsp;Freja Ebeling,&nbsp;Astrid Marta Olsnes,&nbsp;Jan Maxwell Nørgaard,&nbsp;Leonie Saft,&nbsp;Lars Möllgård,&nbsp;Eva Hellström-Lindberg,&nbsp;Brigitte Schlegelberger,&nbsp;Gudrun Göhring","doi":"10.1002/gcc.70029","DOIUrl":"https://doi.org/10.1002/gcc.70029","url":null,"abstract":"<p>In myelodysplastic syndromes (MDS), cytogenetic characteristics of the malignant bone marrow cells influence the clinical course. The aim of this study was to evaluate whether cytogenetics is useful to predict outcome and response in patients with del(5q) under azacitidine (AZA) ± lenalidomide (LEN) therapy. We therefore performed comprehensive cytogenetic analyses in MDS patients with del(5q) treated within the randomized phase II trial NMDSG10B. Seventy-two patients were enrolled in the study and 46 patients (64%) had sufficient cytogenetics at inclusion and response evaluation. Karyotyping was significantly more sensitive during follow-up to detect del(5q) compared to FISH, 34 patients (97%) versus 27 patients (77%) (<i>p</i> = 0.027). The overall response rate (ORR) did not differ between the 11 patients with &lt; 3 aberrations (median 1 aberration) and the 59 patients with ≥ 3 aberrations (median 7 aberrations, range 3–16), while ≥ 3 aberrations were associated with shorter overall survival (OS), 9.9 months versus 25.2 months (<i>p</i> = 0.004). OS was significantly shorter in patients with unbalanced translocation of 5q than patients with del (5)(q14q34), 8.4 months versus 21.1 months (<i>p</i> = 0.004). Both complex karyotype and multi-hit <i>TP53</i> alterations were more frequent in patients with unbalanced translocations of 5q versus del (5)(q14q34), 98% and 88% versus 67% and 47% (each <i>p</i> = &lt; 0.001). Most patients with cytogenetic progression had multi-hit <i>TP53</i> alterations at inclusion. Cytogenetic progression occurred at a similar frequency in the AZA arm and in the AZA + LEN arm. In summary, this study in homogenously treated MDS patients with different abnormalities of 5q demonstrates the influence of cytogenetics on treatment results.</p><p><b>Trial Registration:</b> EudraCT number: 2011-001639-21; ClinicalTrials.gov identifier: NCT01556477.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362540","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 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}