Mohamed Elmoryah, Fatima B. Ergen, John M. Skaugen, Catherine K. Gestrich, Melissa A. Burgess, Kurt R. Weiss, Ivy John
{"title":"Expanding the Spectrum of SRF-Rearranged Myoid Tumors: An Adult Case With SRF::SOHLH1 Fusion and Suspected Metastasis","authors":"Mohamed Elmoryah, Fatima B. Ergen, John M. Skaugen, Catherine K. Gestrich, Melissa A. Burgess, Kurt R. Weiss, Ivy John","doi":"10.1002/gcc.70086","DOIUrl":"10.1002/gcc.70086","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137206","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":"Cytogenetic and Molecular Genetic Driven Prediction of Response to First-Treatment and Prognosis in Acute Myeloid Leukemia: A Retrospective Cohort Study","authors":"Henan Zhang, Xuan Liu, Xiaoning Wang, Qiang Zhang, Beibei Xin, Yiyang Shen, Pengcheng He, Jihong Zhang","doi":"10.1002/gcc.70081","DOIUrl":"https://doi.org/10.1002/gcc.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The first induction therapy is critical in determining subsequent treatment strategies and patient outcomes in acute myeloid leukemia (AML). This study aimed to comprehensively analyze the genetic landscape of AML patients to construct risk prediction models for the first-treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 921 adult AML patients (Cohort 1) were included to characterize the genetic landscape and explore the correlations among genetic features in AML. To ensure the generalizability of the risk prediction models, 62 AML patients (Cohort 2) from another center were included in the modeling analysis. Risk prediction models for the first-treatment response were constructed using multivariable logistic regression with bootstrapping validation, and their impact on prognosis was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cohort exhibited cytogenetic abnormalities, with favorable, intermediate, and adverse-risk features for 15.9%, 67.5%, and 16.5%, respectively. The top mutation genes were <i>NPM1</i>, <i>FLT3-ITD</i>, and <i>NRAS</i>. The top single nucleotide polymorphisms (SNPs) sites were <i>GATA2</i> rs2335052, <i>TP53</i> rs1042522, and <i>TET2</i> rs2454206. Risk assessment models showed that for the intensive chemotherapy group, <i>t</i>(16;16) (p13; q22), <i>CEBPA</i> bZIP in-frame, and <i>NPM1</i> type A were favorable factors, while trisomy 22, <i>TET2</i>, <i>FLT3-ITD</i>, <i>FLT3</i> p.D835, <i>ASXL1</i> rs750318549, and <i>TP53</i> were unfavorable factors. For the non-intensive chemotherapy group, normal karyotypes and all <i>CEBPA</i> mutations were favorable factors. Calibration curves revealed an area under the receiver operating characteristic curve (AUC) of 73.3% for the intensive chemotherapy cohort and 66.1% for the low-intensive chemotherapy cohort. Among non-transplanted patients, significantly longer overall survival (OS) and progression-free survival (PFS) were observed in those predicted to achieve complete remission (CR)/CR with incomplete count recovery (CRi) compared to those predicted to not achieve CR/CRi.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study first explores the combined role of karyotypes, mutations, and SNPs in AML treatment, offering valuable risk prediction models for guiding strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111382","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}
Bartosz Urbański, Karolina Miarka-Walczyk, Zuzanna Urbańska, Marta Wąsikowska, Elżbieta Sałacińska-Łoś, Karolina Bukowska-Strakova, Monika Lejman, Ewelina Jaroszek, Barbara Piątosa, Wojciech Młynarski, Agata Pastorczak, Szymon Janczar
{"title":"IGH::IL3-Rearranged B-Cell Precursor Acute Lymphoblastic Leukemia With Hypereosinophilia in a Child With a Novel PAX5 Germline Variant","authors":"Bartosz Urbański, Karolina Miarka-Walczyk, Zuzanna Urbańska, Marta Wąsikowska, Elżbieta Sałacińska-Łoś, Karolina Bukowska-Strakova, Monika Lejman, Ewelina Jaroszek, Barbara Piątosa, Wojciech Młynarski, Agata Pastorczak, Szymon Janczar","doi":"10.1002/gcc.70080","DOIUrl":"https://doi.org/10.1002/gcc.70080","url":null,"abstract":"<p>B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the t(5;14)(q31;q32) chromosomal translocation resulting in an <i>IGH</i>::<i>IL3</i> fusion is an exceptionally rare lymphoid malignancy presenting with hypereosinophilia. Germline <i>PAX5</i> alterations, including sequence variants and deletions, are associated with a selective susceptibility to BCP-ALL and lymphomas, based on a limited number of affected families worldwide. Here, we report a 6-year-old male with BCP-ALL with the t(5;14)(q31;q32) translocation and harboring a novel constitutional <i>PAX5</i> variant (NM_016734.3:c.[295dup];[=], p.[(Ile99Asnfs*3)];[(=)]). Despite the low representation of the leukemic clone in the bone marrow, the <i>IGH::IL3</i> fusion was identified by both fluorescent in situ hybridization (FISH) and optical genome mapping (OGM). Although hypereosinophilia poses a risk of multiorgan damage, our patient exhibited only pneumonia and asymptomatic neuroimaging alterations in the central nervous system. The patient achieved remission by the end of induction and is currently continuing maintenance therapy. In line with existing literature, familial segregation of the <i>PAX5</i> variant demonstrated high but incomplete penetrance, as two leukemia-free mutation carriers displayed only subclinical B lymphocyte maturation abnormalities without hypogammaglobulinemia. Our report underscores the diagnostic utility of OGM, which unequivocally demonstrated the characteristic translocation. Typically, BCP-ALL in affected family members exhibits secondary somatic aberrations involving the wild-type <i>PAX5</i> allele, including structural variants or loss of heterozygosity (LOH) of chromosome 9p, as well as <i>PAX5</i> somatic mutations. To our knowledge, this is the first human report aligning with animal models, which suggests that secondary alterations activating the JAK–STAT pathway may potentially contribute to leukemogenesis in a <i>PAX5</i> mutation background.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111381","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}
Abbas Agaimy, Josephine K. Dermawan, Elisabete Rios, Norbert Meidenbauer, Arno Dimmler, Robert Stoehr, Cristina R. Antonescu
{"title":"NFATC2::NUTM2A/B Fusions Characterize a Novel Indolent Myoepithelial-Like Neoplasm of the Lungs and Salivary Glands","authors":"Abbas Agaimy, Josephine K. Dermawan, Elisabete Rios, Norbert Meidenbauer, Arno Dimmler, Robert Stoehr, Cristina R. Antonescu","doi":"10.1002/gcc.70083","DOIUrl":"https://doi.org/10.1002/gcc.70083","url":null,"abstract":"<p>With the increasing use of next-generation sequencing, the classification of heretofore unclassified neoplasms is evolving rapidly. Specifically, gene fusions have emerged as context-specific defining genetic markers for an increasing number of entities, mostly of soft tissue, bone, and salivary gland origin. We describe four myoepithelial-like neoplasms of salivary (two) and pulmonary (two) origin, carrying recurrent <i>NFATC2</i> fusions involving <i>NUTM2B</i> (three) and <i>NUTM2A</i> (one) as fusion partners. Patients were two females and two males aged 24–67 years (median, 33). The tumor size ranged from 1 to 4.5 cm. Treatment was surgery without (three) or with (one) adjuvant radiochemotherapy. No metastases or other primary tumors were found at the time of diagnosis. Three patients with follow-up (two with salivary, one with pulmonary tumor) were disease-free at 9, 11, and 31 months. Original diagnoses were “unclassified neoplasm” with consideration of adamantinoma-like Ewing sarcoma and myoepithelial neoplasm. Histology revealed infiltrating monotonous epithelioid to basaloid cells arranged into lobular aggregates, nests, and cords within variably sclerosed stroma containing extensive basement membrane-like hyaline material. Frankly malignant features (malignant cytology, high mitotic activity, necrosis, perineural or lymphovascular invasion) were absent. IHC showed coexpression of low and high molecular weight keratins (AE1/AE3 and CK5/6; 4/4), EMA (2/2), and CD99 (2/2). Negative markers included p63 (0/4), NUT (0/4), S100 (0/4), SOX10 (0/4), p40 (0/2), and SMA (0/2). This study introduces a novel salivary and lung tumor entity driven by <i>NFATC2::NUTM2A/B</i> fusions and displaying myoepithelial-like morphology but imperfect myoepithelial immunophenotype. Report of more cases should shed light on the biological properties and appropriate therapeutic strategies of this novel neoplasm.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038086","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}
Diego M. Montoya-Cerrillo, Mark G. Evans, Andrew Elliott, Renzo Calderon Anyosa, Jaylou Velez Torres, Elizabeth A. Montgomery, Francis J. Hornicek, H. Thomas Temple, Brooke Crawford, Jonathan Trent, Emily E. Jonczak, Gina D'Amato, Andrew E. Rosenberg
{"title":"BCOR-Mutated Conventional and Dedifferentiated Chondrosarcoma: A Clinicopathologic Study","authors":"Diego M. Montoya-Cerrillo, Mark G. Evans, Andrew Elliott, Renzo Calderon Anyosa, Jaylou Velez Torres, Elizabeth A. Montgomery, Francis J. Hornicek, H. Thomas Temple, Brooke Crawford, Jonathan Trent, Emily E. Jonczak, Gina D'Amato, Andrew E. Rosenberg","doi":"10.1002/gcc.70068","DOIUrl":"https://doi.org/10.1002/gcc.70068","url":null,"abstract":"<p>Conventional and dedifferentiated chondrosarcoma encompass a group of malignant neoplasms that produce cartilaginous matrix and arise within or on the surface of bone. Conventional chondrosarcomas are graded on a three-tiered scale, whereas dedifferentiated chondrosarcoma is typically not graded but is considered a high-grade sarcoma and represents the most aggressive subtype with a poor prognosis. <i>IDH1</i> (isocitrate dehydrogenase-1) and <i>I</i><i>DH2</i> (isocitrate dehydrogenase-2) are the most commonly mutated genes in conventional and dedifferentiated chondrosarcoma, followed in frequency by <i>COL2A1</i> and <i>TP53</i>. <i>IDH1/2</i> driver mutations are also commonly found in enchondroma, considered a benign precursor lesion of chondrosarcoma, and other malignancies such as gliomas, cholangiocarcinoma, and acute myeloid leukemia. In acute myeloid leukemia, the presence of concurrent <i>BCOR</i> (BCL-6 corepressor) loss-of-function mutations has been linked to disease relapse and resistance to treatment with IDH inhibitors. After identifying an index case of conventional chondrosarcoma with unusually aggressive clinical evolution, we investigated the clinicopathological features of 12 cases of <i>BCOR</i>-mutated conventional and dedifferentiated chondrosarcomas against a control group of 15 <i>BCOR</i>-wildtype (WT) cases to determine whether <i>BCOR</i>-mutated tumors had patterns of biological progression different from tumors with intact <i>BCOR</i>. All identified <i>BCOR</i> alterations led to loss-of-function by either missense or nonsense mutations. The prevalence of <i>BCOR</i> mutations occurred in 5% of conventional and dedifferentiated chondrosarcoma, and these were associated with larger tumor size (<i>p</i> = 0.024), metastasis at the time of diagnosis (<i>p</i> ≤ 0.001) and higher T category (3–4 vs. 1–2) (<i>p</i> = 0.009). Although larger studies are necessary to clarify the full impact of <i>BCOR</i> mutations on patients with conventional and dedifferentiated chondrosarcoma, our data indicate that <i>BCOR</i> genetic aberrations are associated with adverse clinical features.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038230","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":"LDB1::KMT2A Fusion in a Spindle-Cell Sarcoma: A Case Report","authors":"Zhigan Wang, Ying Zhang, Mingxing Zhu, Jing Zhou, Jingjing Feng, Dongbing Li, Rongjun Mao, Sheng Xiao","doi":"10.1002/gcc.70084","DOIUrl":"https://doi.org/10.1002/gcc.70084","url":null,"abstract":"<div>\u0000 \u0000 <p><i>KMT2A</i>-rearranged sarcomas represent a heterogeneous group of tumors with clinical behaviors ranging from surgical cure to local recurrence and metastasis. Previously reported fusion partners include <i>YAP1</i> and <i>VIM</i>: <i>YAP1::KMT2A::YAP1</i> is associated with sclerosing epithelioid fibrosarcoma (SEF)-like histology, whereas <i>VIM::KMT2A</i> tumors exhibit a small round-to-spindle cell morphology. A third fusion, <i>CBX6::KMT2A::PYGO1</i>, was reported with a spindle-cell morphology somewhat different from the <i>YAP1::KMT2A::YAP1</i> pattern. Here, we describe a novel <i>LDB1::KMT2A</i> fusion in a spindle-cell sarcoma. The case involves a 19-year-old male who presented with an 8 cm mass situated in the left erector spinae muscle. Histopathological examination revealed a biphasic pattern comprising hypercellular fascicular/matted regions and hypocellular fibroma-like areas. Immunohistochemistry revealed diffuse positivity for CD99, SATB2, cyclin D1, BCL2, TLE1, pan-TRK, and NKX2.2, with focal BCOR expression and a Ki-67 proliferation index of approximately 10%. The tumor was negative for MUC4, SS18-SSX, WT1, cytokeratin (CKpan), vimentin, CD34, S-100, SOX10, SMA, STAT6, desmin, and MyoD1. Comprehensive genomic profiling via next-generation sequencing (NGS) identified a novel <i>LDB1::KMT2A</i> fusion, involving exons 1–10 of <i>LDB1</i> and exons 4–36 of <i>KMT2A</i>. The rearrangement was verified using fluorescence in situ hybridization (FISH) and reverse transcription PCR (RT-PCR) techniques. Additionally, a pathogenic BCOR frameshift mutation (c.3203dup, p.E1069Gfs*10) was identified. The patient underwent wide surgical excision and remains disease-free at a 5-month follow-up. This report presents the first known case of an <i>LDB1::KMT2A</i> fusion in a spindle-cell sarcoma, expanding the molecular spectrum of the emerging entity of <i>KMT2A</i>-rearranged sarcomas.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038229","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}
Isidro Machado, Reyes Claramunt, Susana López, Jessica Aliaga, Enrique Garrigós, Isabel Martín, Ignacio Romero, Antonio Llombart-Bosch, José Antonio López-Guerrero
{"title":"Uterine Myxoid Mesenchymal Tumor With a Novel SS18::VEZF1 Gene Fusion, Lacking Worrisome Histological Features","authors":"Isidro Machado, Reyes Claramunt, Susana López, Jessica Aliaga, Enrique Garrigós, Isabel Martín, Ignacio Romero, Antonio Llombart-Bosch, José Antonio López-Guerrero","doi":"10.1002/gcc.70079","DOIUrl":"https://doi.org/10.1002/gcc.70079","url":null,"abstract":"<p>We report a uterine myxoid mesenchymal tumor with a novel <i>SS18::VEZF1</i> gene fusion. The current lesion was identified in a 53-year-old woman who presented with symptomatic “fibroids” showing accelerated growth and heterogeneous morphology on radiologic assessment. Microscopic examination revealed a well-demarcated neoplasm, and the tumor exhibited alternating hypocellular/hyalinized and hypercellular areas, composed of a monomorphic proliferation of spindle, ovoid, and epithelioid cells arranged in sheets. These cells were embedded within either a hyalinized collagenous stroma or abundant myxoid stroma. Tumor cells were frequently located around blood vessels and exhibited amphophilic or eosinophilic cytoplasm and elongated or ovoid-shaped nuclei with coarsely clumped chromatin. No mitoses, pleomorphism, or necrosis was identified. Immunohistochemically, the tumor was positive for CD10, CD34, TLE1, estrogen, and progesterone receptors. It was negative for h-caldesmon, desmin, smooth muscle actin, smoothelin, myosin, cyclin D1, S100, ALK, EMA, panTRK, and SS18-SSX. Targeted RNA sequencing revealed an <i>SS18::VEZF1</i> gene fusion (breakpoint: <i>exon 9</i>–<i>exon 2</i>), which was confirmed by FISH (<i>SS18</i>). In conclusion, RNA sequencing was useful in identifying the fusion event, thereby excluding potential mimics with uncommon morphology or ambiguous immunophenotype.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914896","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}
Vanghelita Andrei, Elena Zheleznyakova, Silvia Cavalchini, Jane Chalker, Michael Hubank, Roberto Tirabosco, Paul O'Donnell, Fernanda Amary, Adrienne M. Flanagan
{"title":"PLAG1-Rearranged Fibromyxoid and Lipomatous Neoplasms in Children and Adults: Separate Entities or a Morphological Spectrum?","authors":"Vanghelita Andrei, Elena Zheleznyakova, Silvia Cavalchini, Jane Chalker, Michael Hubank, Roberto Tirabosco, Paul O'Donnell, Fernanda Amary, Adrienne M. Flanagan","doi":"10.1002/gcc.70070","DOIUrl":"https://doi.org/10.1002/gcc.70070","url":null,"abstract":"<p>Fusions involving the <i>PLAG1</i> gene are associated with multiple cancers and benign tumors, including lipoblastoma and the more recently described pediatric fibromyxoid soft tissue tumor. We report two <i>PLAG1</i>-rearranged mesenchymal tumors arising in adults which, although largely similar histologically to the fibromyxoid tumors reported in infants, display limited adipocytic differentiation. In both cases, the novel fusion partner was <i>DLEU2</i>. Whole genome sequencing of one of the tumors also showed loss of 13p including the <i>RB1</i> locus. Expression of PLAG1 was demonstrated by extensive immunoreactivity in both cases. We discuss the similarities of our cases to the previously described fibroblastic variants of lipoblastomas and the recently reported cases of <i>PLAG1</i>-rearranged fibromyxoid soft tissue tumors, highlighting the overlapping morphological and molecular features. We consider that there is growing evidence that these histological entities are related to conventional lipoblastoma and represent tumors of adipocytic lineage exhibiting different stages of cellular maturation.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894206","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":"Adult Type Lipoblastoma With a Predominantly Fibroblastic Morphology and a Novel DLEU2::PLAG1 Gene Rearrangement: Two Cases of a Rare Entity","authors":"Tyler Steidl, Michael Michal, David I. Suster","doi":"10.1002/gcc.70064","DOIUrl":"https://doi.org/10.1002/gcc.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Lipoblastoma is a benign adipocytic lesion with embryonal fat cell differentiation. The tumors most commonly occur in children, however, rare cases have been reported to occur in adults and are generally considered to represent “maturing” or long-standing lipoblastomas. Approximately 60%–80% of these tumors harbor a gene fusion involving the <i>PLAG1</i> gene, which is known to rearrange with numerous unique fusion partners. Herein, we present two additional cases of so-called maturing lipoblastoma with a review of the literature. Both tumors occurred in adult females and both harbored a yet-unreported <i>DLEU2</i>::<i>PLAG1</i> fusion transcript. Clinically, both tumors behaved in a benign fashion. The histology was characterized by a prominence of fibroblastic growth with only partial or minimal lipomatous components. This report serves to provide additional characterization of the clinical, histologic, and molecular features of this rare tumor type.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894207","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}
Yamato Suemitsu, Hsin-Yi Chang, Carla Saoud, Josephine K. Dermawan, Meera Hameed, Samuel Singer, William D. Tap, Cristina R. Antonescu
{"title":"Secondary Genetic Alterations in Extraskeletal Myxoid Chondrosarcoma","authors":"Yamato Suemitsu, Hsin-Yi Chang, Carla Saoud, Josephine K. Dermawan, Meera Hameed, Samuel Singer, William D. Tap, Cristina R. Antonescu","doi":"10.1002/gcc.70076","DOIUrl":"https://doi.org/10.1002/gcc.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm of uncertain histogenesis, characterized by recurrent gene fusions involving <i>NR4A3</i> with various gene partners (<i>EWSR1</i>, <i>TAF15, FUS</i>, etc.). Although the impact of fusion variants has been linked to histology and prognosis, no study to date has comprehensively investigated the incidence and spectrum of secondary genetic alterations (SGAs) in EMC with regard to their association with fusion type and clinical impact. Our molecular database was searched for EMC tested on a hybridization capture-based targeted matched tumor-normal DNA NGS assay (MSK-IMPACT, 341-505 gene panel). All tumors had their fusion subtype confirmed either by Archer FusionPlex and/or fluorescence in situ hybridization (FISH). Clinicopathologic data was reviewed. Eighteen EMC patients (20 samples) were selected, with a mean age of 61 years and a male: female ratio of 5:1. By molecular testing, the most common <i>NR4A3</i> fusion subtype involved <i>EWSR1</i> (14/18, 78%), while two cases involved <i>TAF15</i> gene partner, and one each <i>TCF12</i> and <i>FUS</i> genes, respectively. All cases showed a low tumor mutation burden (TMB) (0–2, mean 0.83). Two-thirds of cases had concurrent SGAs, while the remaining showed only the driver <i>NR4A3</i> fusion (0–8, mean 1.67 mut/case). Among the detected SGAs, only <i>TP53</i> alterations were recurrent, seen in 2 cases with <i>EWSR1::NR4A3</i> and <i>TAF15::NR4A3</i> fusions, respectively. Other non-recurrent alterations involved <i>CDKN1B</i>, <i>TERT</i>, and <i>MET</i> genes, among others. Non-<i>EWSR1</i> fusion variant tumors showed a tendency for a higher number of SGAs compared to <i>EWSR1</i>-rearranged tumors (mean 2.75 versus 1.36 mut/case). Patients with ≥ 1 SGA showed lower disease-free survival (DFS) (<i>p</i> = 0.022) and poor overall survival (OS) (<i>p</i> = 0.014), while no statistically significant correlation was detected between OS and fusion subtypes. Most patients (83%) developed distant metastases, which did not correlate with the SGA status. This is the first study addressing the genomic landscape in EMC with regard to prognostication beyond fusion subtypes and histology. Similar to other translocation-associated sarcomas, the number of co-occurring SGAs in EMC is low; however, when present, they are associated with worse survival. Although a higher number of SGAs showed a trend to be associated with non-<i>EWSR1</i> fusion variants, larger multi-institutional studies are needed to further evaluate the correlation between fusion variants with SGAs and survival.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 8","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869681","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}