Genes, Chromosomes & Cancer最新文献

{"title":"A Novel MEIS1::NCOA2 Fusion Gene in Acute Myeloid Leukemia.","authors":"Lei Wang, Xincun Zhong, Feng Gao, Xiao Wu, Tingting Lu, Yanfang Wang, Lingling Jiang, Chunyu Gu, Qi Xu, Ping Chen, Qiurong Zhang","doi":"10.1002/gcc.70121","DOIUrl":"10.1002/gcc.70121","url":null,"abstract":"<p><p>MEIS1::NCOA2 is a recurrent fusion gene primarily associated with genitourinary and gynecologic sarcomas, with no reported association with acute myeloid leukemia (AML) to date. We report the first case of AML in a 42-year-old woman with a novel MEIS1::NCOA2 fusion, identified by targeted RNA sequencing and validated by Sanger sequencing. This fusion arises from a t(2;8)(p14;q13.3) translocation that fuses MEIS1 exon 11 to NCOA2 exon 14; its MEIS1 breakpoint differs from the classic exons 6/7 in sarcomas and retains nearly the full-length functional domains of MEIS1 that are critical for leukemogenesis. This case expands the genomic and disease spectrum of MEIS1::NCOA2, identifies a unique AML-associated breakpoint with potential leukemogenic roles, and warrants further functional and therapeutic investigation of this fusion gene.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70121"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147948185","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 Clinicopathologic and Molecular Analysis of Mesenchymal Tumors With BRAF Fusions.","authors":"Maximus C F Yeung, Cristina R Antonescu","doi":"10.1002/gcc.70144","DOIUrl":"10.1002/gcc.70144","url":null,"abstract":"<p><p>BRAF fusions are rare but recurrent driver events in a spectrum of mostly pediatric and young adult mesenchymal soft tissue tumors, including infantile fibrosarcoma, lipofibromatosis-like neural tumors, and other kinase fusion spindle cell neoplasms. Their clinicopathologic spectrum, co-occurring secondary genomic events, and frequency among various sarcoma histotypes remain incompletely characterized. The purpose of this study is to comprehensively investigate the incidence and structural variants of BRAF fusions among a large clinicopathologic and molecular sarcoma cohort. The additional goal was to distinguish primary driver BRAF fusions from potential passenger events and correlate with sarcoma histotypes. We identified a total of 24 cases harboring BRAF fusions, with 18 (75%) occurring in canonical BRAF-driven histotypes, including kinase-associated spindle cell tumors (n = 12), myxoinflammatory fibroblastic sarcoma (n = 3), GIST (n = 2) and one hybrid nerve sheath tumor. The remaining six cases were detected in various established pathologic entities (undifferentiated pleomorphic sarcoma, angiosarcoma, embryonal rhabdomyosarcoma, dedifferentiated liposarcoma, PEComa), likely as secondary or passenger events. Among the 12 kinase-associated spindle cell tumors, the most common histologies included tumors resembling infantile fibrosarcoma (n = 4), malignant peripheral nerve sheath tumor (n = 3), lipofibromatosis (n = 2), and myoid/pericytic lesions (n = 2). This predominant group had a wide age range at diagnosis (median 15.5 years), a predilection for soft tissues of extremities, trunk, and head/neck and showed CD34 and S100 co-expression in 45% of cases. In this group, BRAF breakpoints clustered in exons 8-11 retaining an intact kinase domain, and fusion partners were diverse (AGK, AHNAK, NRF1, PAK2, TMEM245, FNBP1, STEAP4, TSC1, KIAA1549). Tumor mutation burden was consistently low, with CDKN2A homozygous deletion being the only recurrent secondary event (4/5 cases profiled). Among the five patients with follow-up (median 34 months), one patient died of disease, with two developing local recurrences at 5 and 84 months. The BRAF fusions occurring in non-canonical histotypes had similar breakpoint patterns and various partners. These results highlight the heterogeneity of mesenchymal neoplasms harboring BRAF fusions, including both driver and likely secondary genetic events, which often require a comprehensive approach that integrates clinical, histopathologic, and detailed molecular data, for a definitive classification.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70144"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148029407","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 SMARCA4::VEZF1 Rearrangement in Pediatric Sarcomas.","authors":"Libing Fu, Rongjun Mao, Changliang Zhang, Fan Yang, Si Chen, Dan Zhou, Sheng Xiao","doi":"10.1002/gcc.70132","DOIUrl":"10.1002/gcc.70132","url":null,"abstract":"<p><p>The SMARCA4 gene encodes a key ATPase subunit of the SWI/SNF (BAF) chromatin-remodeling complex, which plays an essential role in regulating transcription and cellular differentiation. Loss-of-function alterations of SMARCA4 are common in various human cancers, including sarcomas; however, rare SMARCA4 fusion events, presumably resulting in gain of function, have also been reported. We present two pediatric soft-tissue sarcomas harboring a novel, recurrent in-frame fusion between SMARCA4 and VEZF1 (Vascular Endothelial Zinc Finger 1), a transcription factor important for vascular development and angiogenesis. The predicted fusion protein contains the N-terminal QLQ protein interaction domain of SMARCA4 and preserves most of VEZF1's C2H2 zinc-finger DNA-binding domains. Interestingly, another component of the BAF complex, SS18, has also been reported to be fused to VEZF1 in uterine sarcoma. We propose that fusion of BAF complex components to VEZF1 leads to aberrant recruitment of chromatin-remodeling activity to VEZF1 target loci, resulting in altered chromatin architecture, dysregulated VEZF1-dependent transcription, and tumorigenesis.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70132"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837210","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 Fusion Gene Transcripts and Targetable Mutations in High-Risk B-ALL With Exceptional Response to Venetoclax-Based Therapy.","authors":"Jifang Tu, Huanping Wang, Yungui Wang, Junhao Zhou, Xiangli Gao, Yinjun Lou, Hongyan Tong","doi":"10.1002/gcc.70134","DOIUrl":"10.1002/gcc.70134","url":null,"abstract":"<p><p>Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous malignancy characterized by a broad spectrum of chromosomal and gene abnormalities that define distinct genetic subtypes driving disease development. Although numerous driver fusion genes have been documented, a considerable proportion of ALL cases remain inadequately defined, classified, and consequently lack access to precisely targeted therapies. Herein, we report a case of high-risk B-ALL harboring four novel fusion gene transcripts-MAN1A1::GRIK2, ZCCHC7::CASC11, OSTM1-AS1::ZBTB24, and IGL::BCL6-along with concurrent mutations in CREBBP, BCL2, and ARID1B. These four novel fusion genes, particularly the BCL6 rearrangement, may represent a genetic feature that warrants further investigation in B-ALL. The patient received induction therapy with a modified COP regimen (cyclophosphamide, vindesine, dexamethasone) combined with the BCL2 inhibitor venetoclax, achieving a rapid and sustained complete remission. This case suggests that integrating deep genomic analysis can help identify potentially actionable therapeutic targets and provides preliminary clinical evidence supporting the efficacy of modified COP plus venetoclax in high-risk B-ALL with similar molecular features, highlighting a promising precision medicine strategy.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70134"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873870","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":"Clear Cell Chondrosarcoma With Somatic VHL Inactivation: A Case Report With Integrated Genomic and Transcriptomic Analysis.","authors":"Lalit R Patel, Philip Wong, Shervin Oskouei, Armita Bahrami","doi":"10.1002/gcc.70130","DOIUrl":"10.1002/gcc.70130","url":null,"abstract":"<p><strong>Background: </strong>Clear cell chondrosarcoma (CCC) is a rare, low-grade malignant bone tumor and a specific subtype of chondrosarcoma. In contrast to conventional central chondrosarcoma, which often exhibits recurrent IDH1/2 mutations, CCC is IDH-wildtype, and its genomic profile remains uncharacterized. Sporadic cases have been described in association with von Hippel-Lindau (VHL) disease, but somatic VHL alterations have not been demonstrated in this tumor.</p><p><strong>Methods: </strong>A 35-year-old man presented with local recurrence of a distal femoral tumor 5 years after curettage and allograft reconstruction for a tumor that was initially diagnosed as clear cell chondrosarcoma. The recurrent tumor was resected and analyzed using a comprehensive DNA/RNA next-generation sequencing assay with matched germline testing to distinguish somatic from germline alterations.</p><p><strong>Results: </strong>The recurrent tumor measured 5.0 cm and showed classic CCC morphology with focal areas of conventional chondrosarcoma-like differentiation. No IDH1/2 mutations were identified. Two pathogenic loss-of-function variants were detected: COL2A1 c.1262_1266+2delinsTCC (variant allele frequency [VAF], 34%) and VHL c.341-2A>C (VAF, 45%). The tumor had a low tumor mutational burden, low loss of heterozygosity, and a complex karyotype with monosomy of chromosome 3. Gene expression profiling revealed decreased VHL mRNA expression. Germline testing showed no germline VHL alteration, confirming somatic VHL inactivation.</p><p><strong>Conclusion: </strong>To our knowledge, this report is the first to describe a molecularly profiled CCC with somatic VHL inactivation. These results expand the evolving genomic spectrum of CCC beyond its previously known IDH-wildtype status and suggest that VHL pathway dysregulation may contribute to tumorigenesis in a subset of cases.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70130"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837213","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":"The t(X;5)(q13;q33) Translocation in Myeloid Neoplasms Is Preferentially Associated With Chronic Myelomonocytic Leukemia: A Report From the Groupe Francophone de Cytogénétique Hématologique.","authors":"Florence Nguyen-Khac, Marc Muller, Agnes Daudignon, Thomas Smol, Giulia Tueur, Antoine Ittel, Catherine Settegrana, Jean-Francois Lesesve, Audrey Bidet, Pierre Hirsch","doi":"10.1002/gcc.70143","DOIUrl":"10.1002/gcc.70143","url":null,"abstract":"<p><p>t(X;5)(q13;q33) is a very rare but recurrent translocation observed in hematological malignancies. Only two myeloid cases have been reported in the literature to date. In one case, it was demonstrated that the t(X;5) involves the inactive X chromosome and is associated with silencing of autosomal genes located on 5q. Here, we report four additional cases. Overall, t(X;5) is frequently associated with chronic myelomonocytic leukemia (CMML) (4/6 cases, 67%) and may have functional consequences similar to those of del(5q). In contrast to del(5q) in CMML, which is often associated with a complex karyotype, t(X;5) is most often observed as an isolated abnormality and may define a distinct subgroup with favorable genetic features. Additional cases and functional studies are needed to confirm our observations.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70143"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005261","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":"Complex Karyotype in CLL-How to Count Cytogenetic Aberrations Consistently and Efficiently.","authors":"Alessandro Baldi, Anna Stengel, Martha-Lena Müller, Gregor Hoermann, Wolfgang Kern, Isolde Summerer","doi":"10.1002/gcc.70129","DOIUrl":"10.1002/gcc.70129","url":null,"abstract":"<p><p>Complex karyotype (CK) in chronic lymphocytic leukemia (CLL), defined by ≥ 3 or ≥ 5 (high-CK) chromosomal aberrations, is an established adverse prognostic marker. However, different methods for counting aberrations are used in the literature and clinical trials, potentially affecting CK classification and risk stratification. We systematically compared two established counting methods: the approach by Jondreville et al., which counts one aberration per item separated by commas, and the International System for Human Cytogenomic Nomenclature (ISCN) method, which counts unbalanced aberrations involving multiple chromosomes as two aberrations. Chromosome banding analyses from 1605 CLL patients were evaluated using both counting methods. This revealed that CK classification by the two methods disagreed in 7.5% of all cases. However, both methods performed similarly in prognostic stratification of these ambiguous cases. This suggests that the method proposed by Jondreville et al. should be adopted, as it is simpler to perform and less ambiguous. Furthermore, we compared how cases were stratified if aberrations are counted across all (sub)clones (as suggested both by Jondreville et al. and the ISCN) or only in the clone with the most aberrations. In total, 3.5% of all cases were differentially classified depending on whether aberrations were counted across all clones or only in the most complex clone. Importantly, these ambiguous cases were better stratified by counting aberrations in the most complex clone only. We therefore suggest the method proposed by Jondreville et al. to determine CK status in CLL and to count aberrations only in the clone with the most aberrations.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":"e70129"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837186","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148088188","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148086470","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148080505","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}