Genes, Chromosomes & Cancer最新文献

{"title":"SMARCA4 Deficiency in Lung Cancer: From Signaling Pathway to Potential Therapeutic Targets","authors":"Mingzhu Zhang,&nbsp;Youhong Dong,&nbsp;Rui Meng,&nbsp;Dongdong Zhang","doi":"10.1002/gcc.70022","DOIUrl":"10.1002/gcc.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>SMARCA4-deficient lung cancer, including thoracic SMARCA4-deficient undifferentiated tumors and SMARCA4-deficient nonsmall-cell lung carcinomas, is a rare and aggressive disease characterized by rapid progression and poor prognosis. This cancer was identified as a distinct entity with specific morphologic and molecular features in the 2021 WHO Classification of Thoracic Tumors. Molecular alterations in SMARCA4 are specific to this type of lung cancer. Deficiency in SMARCA4 suppresses the SWI/SNF tumor suppressor complex, driving tumor progression. Due to the lack of standardized treatment, most patients succumb to the disease within 6 months. This study provides a detailed analysis of the SMARCA4 pathway and its role in lung cancer. We analyzed potential therapeutic targets and agents to offer insights for the precise and effective treatment of SMARCA4-deficient lung cancer.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983294","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":"The Transcriptomic and Gene Fusion Landscape of Pleomorphic Salivary Gland Adenomas","authors":"Maryam Kakay Afshari,&nbsp;Paloma Tejera Nevado,&nbsp;André Fehr,&nbsp;Junchi Huang,&nbsp;Fredrik Jäwert,&nbsp;Jonas A. Nilsson,&nbsp;Göran Stenman,&nbsp;Mattias K. Andersson","doi":"10.1002/gcc.70023","DOIUrl":"10.1002/gcc.70023","url":null,"abstract":"<p>Pleomorphic adenoma (PA) is the most common salivary gland tumor. PAs are characterized by chromosomal rearrangements of 8q12 and 12q14-15, leading to gene fusions involving the <i>PLAG1</i> and <i>HMGA2</i> oncogenes. Here, we performed the first comprehensive study of the transcriptomic and gene fusion landscape of 38 cytogenetically characterized PAs. RNA-seq identified <i>PLAG1</i> or <i>HMGA2</i> fusions in 33/38 cases (87%), of which 15 were novel fusions. Fusions were found also in tumors with normal karyotype, demonstrating that they are generated by cryptic rearrangements. <i>PLAG1</i> was mainly activated by promoter swapping and <i>HMGA2</i> by truncation of its 3′-part. RNA-seq revealed upregulation of genes involved in extracellular matrix production, WNT-signaling, and epithelial-mesenchymal transition in PA compared to normal salivary tissue. Principal component analysis identified two PA subclusters characterized by <i>PLAG1</i>- and <i>HMGA2</i>-activation, respectively, that differed in expression of genes involved in the immune system, cell adhesion, and microenvironment remodeling. Moreover, comparative analyses of PA and salivary carcinomas revealed that PA resembles myoepithelial carcinoma. Our study reveals new oncogenic gene fusions and expands our knowledge about the molecular underpinnings of PA.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983295","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 Challenging Case of an Intraosseous Composite Hemangioendothelioma of the Occipital Bone With YAP1::FOXR1 Fusion","authors":"Fleur Cordier,&nbsp;Liesbeth Ferdinande,&nbsp;Siebe Loontiens,&nbsp;Joni Van der Meulen,&nbsp;Jo Van Dorpe,&nbsp;David Creytens","doi":"10.1002/gcc.70016","DOIUrl":"10.1002/gcc.70016","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 12","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785051","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":"Epigenetic Modeling of Jumping Translocations of 1q Heterochromatin in Acute Myeloid Leukemia After 5'-Azacytidine Treatment","authors":"Anair Graciela Lema Fernandez,&nbsp;Carlotta Nardelli,&nbsp;Valentina Pierini,&nbsp;Barbara Crescenzi,&nbsp;Fabrizia Pellanera,&nbsp;Caterina Matteucci,&nbsp;Maria Crocioni,&nbsp;Silvia Arniani,&nbsp;Valeria Di Battista,&nbsp;Martina Quintini,&nbsp;Giada Mondanelli,&nbsp;Ciriana Orabona,&nbsp;Paolo Gorello,&nbsp;Cristina Mecucci","doi":"10.1002/gcc.70013","DOIUrl":"10.1002/gcc.70013","url":null,"abstract":"<p>Jumping translocations (JT) are rare cytogenetic abnormalities associated with progression in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Typically, a tri–tetra-somic 1q chromosome is translocated to two or more recipient chromosomes. In multiple myeloma JT were shown to originate after DNA demethylation and decondensation. Using epigenomics, we investigated sequential samples in an <i>SRSF2</i>-mutated MDS and AML cohort with normal karyotype at diagnosis and 1qJT at disease evolution after 5′-azacytidine (AZA). 1qJT breakpoints fell within repetitive DNA at both 1q12 and the translocation partners, namely acrocentrics n. 14, 15, 21, and 22, chromosome 16, and chromosome Y. The global methylome at diagnosis showed hypermethylation at 61% of the differentially methylated regions (DMRs), followed by hypomethylation at 80% of DMRs under AZA, mostly affecting pathways related to immune system, chromatin organization, chromosome condensation, telomere maintenance, rRNA, and DNA repair. At disease evolution, a shift toward hypermethylation, intronic enhancers enrichment and epigenetic involvement of the PI3K/AKT and MAPK signaling emerged. In particular, AKT1 phosphorylation behaved as a hallmark of the progression. Overall, we provided new insights on the characterization of 1qJT in <i>SRSF2</i>-mutated myeloid neoplasms and first showed that epigenetics is a powerful tool to investigate the molecular landscape of repetitive DNA rearrangements.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739271","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":"Malignant Bone-Forming Neoplasm With NIPBL::BEND2 Fusion","authors":"Nooshin K. Dashti,&nbsp;George Matcuk,&nbsp;Abbas Agaimy,&nbsp;Carla Saoud,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.70015","DOIUrl":"10.1002/gcc.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Conventional high-grade osteosarcomas are characterized by aggressive radiologic features, cytologic pleomorphism, and complex genomics. However, rare examples of osteosarcomas remain challenging due to unusual histology, such as sclerosing or osteoblastoma-like features, which may require molecular confirmation of their complex genetic alterations. We have encountered such a case in a 17-year-old man, who presented with a third metatarsal sclerotic bone lesion, found incidentally in the work-up of a foot trauma. The initial imaging revealed a lesion with sclerotic/blastic features proximally and lucent/lytic portion distally, findings interpreted consistent with osteoblastoma. The lesion was managed intra-lesionally with curettings and cryoablation; however, the microscopic findings were non-specific, showing a bland osteoblastic proliferation embedded in a densely sclerotic matrix. Subsequently, the patient developed two rapid recurrences; the first recurrence was treated similarly despite its associated soft tissue extension radiographically, and the histologic findings remained non-specific. The 2nd recurrence showed a large mass, with bone destruction and soft tissue extension and an open biopsy revealed features of osteosarcoma with lace-like osteoid deposition, albeit with uniform cytomorphology. The subsequent below knee amputation showed features compatible with high-grade osteosarcoma, including solid growth of uniform epithelioid cells, with vesicular nuclei and scant cytoplasm, set in a lace-like meshwork of osteoid matrix. There was significant mitotic activity and tumor necrosis. Tumor cells were positive for SATB2. Further molecular work-up was performed showing an unexpected <i>NIPBL::BEND2</i> fusion, which has been previously reported in two cases of phosphaturic mesenchymal tumor (PMT). FGF23 (ISH) was performed and was negative. By DNA methylation profiling, unsupervised clustering and UMAP dimensionality reduction revealed grouping with high-grade osteosarcomas and not with the PMT group. The patient received chemotherapy post-amputation and is alive without evidence of disease, with 10-month follow-up. We report an aggressive, overtly malignant acral bone-forming tumor, harboring a <i>NIPBL::BEND2</i> fusion. Further studies are needed to evaluate the recurrent potential of this fusion in osteosarcomas and its relationship with PMT.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739273","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":"Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets","authors":"Shuhao Fan,&nbsp;Jianhua Guo,&nbsp;Hui Nie,&nbsp;Huabao Xiong,&nbsp;Yong Xia","doi":"10.1002/gcc.70008","DOIUrl":"https://doi.org/10.1002/gcc.70008","url":null,"abstract":"<p>Energy metabolic reprogramming is frequently observed during tumor progression as tumor cells necessitate adequate energy production for rapid proliferation. Although current medical research shows promising prospects in studying the characteristics of tumor energy metabolism and developing anti-tumor drugs targeting energy metabolism, there is a lack of systematic compendiums and comprehensive reviews in this field. The objective of this study is to conduct a systematic review on the characteristics of tumor cells' energy metabolism, with a specific focus on comparing abnormalities between tumor and normal cells, as well as summarizing potential targets for tumor therapy. Additionally, this review also elucidates the aberrant mechanisms underlying four major energy metabolic pathways (glucose, lipid, glutamine, and mitochondria-dependent) during carcinogenesis and tumor progression. Through the utilization of graphical representations, we have identified anomalies in crucial energy metabolism pathways, encompassing transporter proteins (glucose transporter, CD36, and ASCT2), signaling molecules (Ras, AMPK, and PTEN), as well as transcription factors (Myc, HIF-1α, CREB-1, and p53). The key molecules responsible for aberrant energy metabolism in tumors may serve as potential targets for cancer therapy. Therefore, this review provides an overview of the distinct energy-generating pathways within tumor cells, laying the groundwork for developing innovative strategies for precise cancer treatment.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708377","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":"Peter Besmer, PhD Obituary (1940–2024)","authors":"Cristina Antonescu","doi":"10.1002/gcc.70014","DOIUrl":"https://doi.org/10.1002/gcc.70014","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708339","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":"Fibromyxoid aSoft Tissue Tumor With PLAG1 Fusion—The First Case in an Adult Patient","authors":"M. Strnadová,&nbsp;J. Balko,&nbsp;P. Brož,&nbsp;L. Wagenknecht,&nbsp;L. Krsková","doi":"10.1002/gcc.70011","DOIUrl":"10.1002/gcc.70011","url":null,"abstract":"<p>With the expanding possibilities of human genome research in recent years, the number of cases of soft tissue tumors that we are able to classify into the correct subgroups and to reveal their molecular profile is increasing. Among such tumors, we can also consider neoplasms that have a specific fusion of genes, in our case namely the pleomorphic adenoma gene 1 (<i>PLAG1)</i> and its partner. <i>PLAG1</i> gene fusions were previously associated mainly with salivary gland pleomorphic adenomas, lipoblastomas, myoepithelial tumors, uterine epitheloid, myxoid leiomyosarcomas, and, recently, with PLAG1-rearranged fibromyxoid soft tissue tumors. To our knowledge, we report the first case of a soft tissue tumor with a <i>PLAG1</i> fusion gene in an adult. In our case, we detected a new <i>H3-3B::PLAG1</i> fusion in a soft tissue tumor, which originally appeared as nodular fasciitis.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686796","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":"An Inflammatory Myofibroblastic Tumor With a Novel ALKV1180L Mutation Leading to Acquired Resistance to Tyrosine Kinase Inhibitors","authors":"Brittney Sharpe,&nbsp;Donald C. Green,&nbsp;Laura J. Tafe,&nbsp;Garrett T. Wasp,&nbsp;Darcy A. Kerr,&nbsp;Nooshin K. Dashti","doi":"10.1002/gcc.70012","DOIUrl":"10.1002/gcc.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that can locally recur and potentially metastasize. Approximately 50% of IMTs harbor rearrangements in the gene encoding anaplastic lymphoma kinase (<i>ALK</i>), a receptor tyrosine kinase that can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). With successful application of TKI in ALK-positive nonsmall cell carcinoma (NSCLC), ALK inhibitors are often first-line treatments for patients with unresectable or metastatic IMTs. Although acquired resistance to these agents may develop, resistance mechanisms are sparsely reported for IMTs. Here we report a case of a 71 year-old man with metastatic pulmonary IMT harboring a <i>DCTN1::ALK</i> fusion that progressed during alectinib TKI treatment. Whole exome sequencing of an enlarging metastatic lesion in right 4th rib revealed a novel p.V1180L mutation in the <i>ALK</i> tyrosine kinase domain as the mechanism of acquired resistance. To our knowledge, this is the first report of acquired p. V1180L mutation in IMTs treated with TKIs. In cases of ALK-positive IMTs that progress on TKI therapy, targeted sequencing for acquired <i>ALK</i> mutations may inform clinical decisions to adopt second-line therapeutic strategies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675626","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 HMGA2::COL14A1 Fusion Identified in Xanthogranulomatous Epithelial Tumor/Keratin-Positive Giant Cell Tumor","authors":"Carina A. Dehner,&nbsp;Darya Buehler,&nbsp;Christopher Hofich,&nbsp;Kevin C. Halling,&nbsp;Andrew L. Folpe","doi":"10.1002/gcc.70010","DOIUrl":"10.1002/gcc.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Xanthogranulomatous epithelial tumor (XGET)/Keratin-positive giant cell tumor (KP-GCT) represents a spectrum of recently described neoplasms characterized by a proliferation of distinctive mononuclear cells expressing keratin within a background of osteoclast-like giant cells, mixed inflammatory cells, and a variably prominent xanthogranulomatous component. Recent studies demonstrated a recurrent <i>HMGA2::NCOR2</i> fusion in many cases. We herein describe a case of XGET/KP-GCT arising in the right femoral head of a 19-year-old male harboring a rare novel <i>HMGA2::COL14A1</i> fusion.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647332","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}