Genes, Chromosomes & Cancer最新文献

{"title":"A Challenging Case of an Intraosseous Composite Hemangioendothelioma of the Occipital Bone With YAP1::FOXR1 Fusion","authors":"Fleur Cordier, Liesbeth Ferdinande, Siebe Loontiens, Joni Van der Meulen, Jo Van Dorpe, 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}

{"title":"Pediatric Mesenchymal Tumor With MN1::TAF3 Fusion","authors":"Chikako Sato,&nbsp;Masanaka Sugiyama,&nbsp;Taisuke Mori,&nbsp;Shogo Nishino,&nbsp;Kayoko Tao,&nbsp;Chitose Ogawa,&nbsp;Akihiko Yoshida","doi":"10.1002/gcc.70009","DOIUrl":"10.1002/gcc.70009","url":null,"abstract":"<div>\u0000 \u0000 <p><i>MN1</i> fusion is emerging as oncogenic in soft-tissue tumors. Here, we provided detailed clinicopathological documentation of a tumor with <i>MN1</i>::<i>TAF3</i> fusion. The tumor developed on the face of an 8-year-old boy and did not recur or metastasize for 5 years after surgery without adjuvant therapy. Histologically, the tumor predominantly comprised sheets and nests of atypical, mildly pleomorphic epithelioid cells. Mallory body-like eosinophilic cytoplasmic inclusions, small round cells, and fascicles of spindle cells were focally observed. Mitotic activity was high, and focal necrosis was present. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3 in the epithelioid cell component but otherwise showed nonspecific phenotypes. Targeted RNA sequencing identified an in-frame <i>MN1</i> (exon 1)::<i>TAF3</i> (exon 3) fusion transcript. We validated the transcript with reverse transcription-polymerase chain reaction, Sanger sequencing, and <i>MN1</i> break-apart fluorescence in situ hybridization. <i>MN1</i>::<i>TAF3</i> was previously listed without details in a large-scale sequencing study involving a pediatric round cell sarcoma in the orbit, raising the possibility that these tumors might form a coherent group.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638640","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":"Differential Expression of Proteins and Genes at the Tumor-Brain Interface in Invasive Meningioma","authors":"Kornwika Senglek,&nbsp;Chinachote Teerapakpinyo,&nbsp;Nutchawan Jittapiromsak,&nbsp;Pakrit Jittapiromsak,&nbsp;Irin Lertparinyaphorn,&nbsp;Paul Scott Thorner,&nbsp;Shanop Shuangshoti","doi":"10.1002/gcc.70007","DOIUrl":"10.1002/gcc.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Most meningiomas are dural-based extra-axial tumors in close contact with the brain. Expression of genes and proteins at the tumor-brain interface in brain-invasive meningioma is basically unknown. Using the NanoString pan-cancer panel, differential expression of genes in the invasive edge versus main tumor body was determined in 12 invasive meningiomas (comprising the discovery cohort), and 6 candidate genes: <i>DTX1</i>, <i>RASGRF1</i>, <i>GRIN1</i>, <i>TNR</i>, <i>IL6</i>, and <i>NR4A1</i>, were identified. By immunohistochemistry, DTX1 and RASGRF1 expression correlated with gene expression, and were studied in an expanded cohort of 21 invasive and 15 noninvasive meningiomas, together with Ki-67. Significantly higher expression of DTX1, RASGFR1, and Ki-67 was found in the invasive edge compared with the main tumor body. Increased expression of RASGRF1 and Ki-67 was more clearly associated with brain invasion. The situation with DTX1 was less definitive since increased expression was observed in meningiomas both at the invasive edge and when in close contact with brain but without invasion. Pathway analyses identified significant links between <i>DTX1</i> and <i>RASGRF1</i> and key biological processes, including cell–cell adhesion, and signaling pathways including Notch, RAS, MAPK, and Rho. Higher expression of DTX1, RASGRF1, and Ki-67 in the brain-invasive area of meningiomas suggests that these proteins play a role in the process of brain invasion.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618635","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}