Genes, Chromosomes & Cancer最新文献

{"title":"Complex Genomic Alterations in TP53-Mutated Myelodysplastic Syndrome and Acute Myeloid Leukemia Involving EPOR/JAK2 Amplification, ERG Copy Gains, and TCF3 Deletion","authors":"T. L. Gindina,&nbsp;S. S. Riumin,&nbsp;I. M. Barkhatov,&nbsp;T. Yu Gracheva,&nbsp;D. S. Bug,&nbsp;E. V. Babenko,&nbsp;E. V. Morozova,&nbsp;N. Yu Tsvetkov,&nbsp;N. N. Mamaev,&nbsp;A. D. Kulagin","doi":"10.1002/gcc.70159","DOIUrl":"10.1002/gcc.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) harboring <i>TP53</i> mutations are defined by extreme genomic instability, complex karyotypes (CK), and poor prognosis. While large-scale chromosomal imbalances are common in CK-MDS/AML, the synergy between focal amplifications of signaling drivers and the disruption of transcriptional regulators remains poorly elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a comprehensive clinical, cytogenetic (GTG-banding, M-FISH, M-Band), and molecular (targeted FISH, NGS) analysis of seven patients with MDS and AML characterized by a recurrent and distinct genomic signature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All cases exhibited highly complex karyotypes on a <i>TP53</i>-mutated background. We identified high-level focal amplifications of <i>EPOR</i> (19p13.2) and <i>JAK2</i> (9p24.1), predominantly manifesting as homogeneously staining regions (HSRs) or complex “sandwich-like” derivative chromosomes. Notably, these signaling alterations consistently co-occurred with monoallelic deletions of the <i>TCF3</i> (<i>E2A</i>) tumor suppressor (19p13.3) and copy number gains of the <i>ERG</i> transcription factor (21q22). Detailed structural analysis indicates that <i>TCF3</i> loss likely arises as a structural consequence of chromosome 19 rearrangements driving <i>EPOR</i> amplification. Based on this data, we propose a conceptual model of leukemogenesis where <i>EPOR/JAK2</i> co-amplification potentially drives constitutive JAK2/STAT5 signaling, while concurrent <i>ERG</i> gain and <i>TCF3</i> haploinsufficiency contribute to maturation delay. <i>TP53</i> deficiency appears to be the primary permissive factor enabling the stabilization of these massive structural rearrangements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings outline a recurrent and biologically coherent genomic pattern within the spectrum of <i>TP53</i>-mutated myeloid neoplasms, demonstrating significant phenotypic overlap with erythroid leukemia features in a subset of cases. Given the small cohort size, these findings are hypothesis-generating. However, this convergence of predicted JAK2/STAT5 pathway hyperactivation and transcriptional disinhibition points to a theoretical therapeutic vulnerability that warrants prospective validation in larger collaborative studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689114","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":"Chondroid Soft Tissue Tumors With FOS::PABPN1 Fusion: A New Entity? About Two Cases","authors":"Jinane Kharmoum,&nbsp;Alexendra Meurgey,&nbsp;Daniel pissaloux,&nbsp;Sanae Chaib,&nbsp;Nicolas Macagno,&nbsp;Mariame Chraibi,&nbsp;Franck Tirode,&nbsp;Marie Karanian","doi":"10.1002/gcc.70157","DOIUrl":"10.1002/gcc.70157","url":null,"abstract":"<p>Soft tissue tumors with chondroid matrix represent a heterogeneous group with persistent diagnostic challenges. Advances in molecular diagnostics have identified recurrent gene fusions in several chondroid neoplasms, predominantly involving <i>FN1.</i> Here, we report two cases of chondroid tumors harboring a novel <i>FOS::PABPN1</i> fusion. The patients were young and presented with small, deep, peri-osseous nodules located in the extremities. Histologically, the tumors were well-circumscribed and lobulated. Both cases presented fibro-cartilaginous and spindle cell areas. No cytonuclear atypia, mitoses, or necrosis were observed. Immunohistochemistry (performed in Case 2) revealed positivity for <i>S100, CD34,</i> and <i>FOS</i>, with negativity for <i>MDM2, HMGA2</i>, <i>PLAG1</i>, and desmin. RNA sequencing identified an identical in-frame <i>FOS::PABPN1</i> fusion transcript in both tumors. Unsupervised transcriptomic clustering positioned the cases near synovial chondromatoses and other chondroid lesions, despite the absence of <i>FN1</i> rearrangements. Massive overexpression of the <i>WIF1</i> (<i>Wnt</i> Inhibitory Factor1) gene was also observed. To our knowledge, this is the first description of FOS rearrangement in mesenchymal tumors exhibiting chondroid differentiation. The <i>FOS::PABPN1</i> fusion expands the spectrum of <i>FOS</i>-altered neoplasms beyond osteoblastic and vascular lesions and defines a potential new molecular subset of benign chondroid tumors. These findings highlight the utility of RNA sequencing in the diagnosis of chondroid neoplasms in order to identify rearrangement (of <i>FN1, THBS1</i> or <i>FOS</i>) or <i>IDH1/2.</i> The consistent upregulation of <i>WIF1</i> may represent a potential diagnostic biomarker.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684390","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":"DNA Hypomethylation Is Not Cell Intrinsically Toxic to Polycomb Repressive Complex 2 Deficient Malignant Peripheral Nerve Sheath Tumors","authors":"Madilyn R. Stahl,&nbsp;Christopher M. Stehn,&nbsp;Zachary J. Seeman,&nbsp;Christopher Faulk,&nbsp;David A. Largaespada","doi":"10.1002/gcc.70156","DOIUrl":"10.1002/gcc.70156","url":null,"abstract":"<p>Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas and the most common cause of disease-associated death for neurofibromatosis type 1 (NF1) patients. In the context of NF1, MPNSTs develop from benign premalignant precursors and the transition to malignancy is typically accompanied by loss of the polycomb repressive complex 2 (PRC2), which results in aberrant upregulation of over 1200 genes due to global depletion of histone H3 lysine 27 trimethylation (H3K27me3). Previous studies suggest cells compensate for the loss of this repressive histone mark via hypermethylation of the genome. Here we analyzed genome-wide DNA methylation and the transcriptome in MPNST cell lines and isogenic PRC2-deficient and -proficient CRISPR-engineered immortalized human Schwann cells. In addition to effects of PRC2 status, we also measured the effects of two DNA methyltransferase inhibitors (DNMTi), decitabine and azacitidine. We found that PRC2 status does not affect global DNA methylation or average methylation levels across specific genomic features. Furthermore, decitabine and azacitidine have differential effects on MPNSTs. While both DNMTis hypomethylate the genome, they upregulate different targets. Azacitidine upregulates genes involved in RNA processing pathways and exhibits direct tumor cell cytotoxicity, while decitabine upregulates genes involved in the immune response, has no direct-cell killing effects, and likely suppresses tumor growth in vivo by altering the tumor microenvironment. We show that DNA hypomethylation alone is insufficient to kill MPNST cells, regardless of PRC2 status. Consequently, these findings suggest that DNMT inhibitors should be utilized in combination with other targeted therapies for MPNST patients.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673521","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":"Accurate Prediction of Central Conventional Chondrosarcoma Risk and Outcome Using Methylation Profiling: CHROME","authors":"Sara Cardoso,&nbsp;Baptiste Ameline,&nbsp;Sanne Venneker,&nbsp;Debora M. Meijer,&nbsp;Zeynep B. Erdem,&nbsp;Dina Ruano,&nbsp;Brendy E. van den Akker,&nbsp;Anne-Marie Cleton-Jansen,&nbsp;Jon Brugger,&nbsp;Inge H. Briaire-de Bruijn,&nbsp;Claire H. J. Scholte,&nbsp;Michiel A. J. van de Sande,&nbsp;Felix Haglund de Flon,&nbsp;Daniel Baumhoer,&nbsp;Noel F. C. C. de Miranda,&nbsp;Judith V. M. G. Bovée","doi":"10.1002/gcc.70160","DOIUrl":"10.1002/gcc.70160","url":null,"abstract":"<p>Chondrosarcomas are malignant cartilage-forming bone tumors with heterogeneous behavior, making prognostication and clinical management challenging. Histological grading is the primary tool for predicting clinical outcomes in conventional chondrosarcoma. However, its high interobserver variability limits reliable distinction between low- and high-risk patients, potentially leading to suboptimal clinical management. Given the increasing use of DNA methylation profiling as a valuable tool in surgical pathology for tumor classification, we investigated its prognostic value in central conventional chondrosarcoma. We generated methylation data from 69 primary central conventional chondrosarcomas profiled with Illumina's <i>Human MethylationEPIC Array</i> (850 k sites), and identified methylation sites individually linked to patient outcome. A LASSO Cox regression model was applied to these methylation sites to identify an optimal set of eight informative sites. With the regression coefficients of these methylation sites, we constructed a risk score that predicts central conventional Chondrosarcoma Risk Outcome from Methylation (CHROME). CHROME stratifies patients into <i>High</i> or <i>Low risk</i> groups for disease recurrence, onset of metastasis and disease-specific mortality. Survival analysis in an independent validation cohort (<i>n</i> = 68) demonstrated strong discriminatory performance of CHROME, with complete separation of outcomes and no adverse events observed in the <i>Low risk</i> group. Overview of the clinico-pathological information showed that a low grade (ACT/G1) case with an event was correctly assigned to the <i>High risk</i> group, while nine high grade cases without events were classified as <i>Low risk</i>. CHROME provides accurate risk stratification in central conventional chondrosarcoma and may represent a valuable tool for improving its prognostication and clinical management.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673485","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":"Nodular Necrotizing Fibroblastic Sarcoma and Myxoinflammatory Fibroblastic Sarcoma: A Comparative Clinicopathological, Molecular, and Epigenetic Study","authors":"Peipei Zhu,&nbsp;Dongyan Han,&nbsp;Yuefang Sun,&nbsp;Qianming Bai,&nbsp;Xiaoyan Zhou,&nbsp;Jian Wang","doi":"10.1002/gcc.70158","DOIUrl":"https://doi.org/10.1002/gcc.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is morphological overlap between nodular necrotizing fibroblastic sarcoma (NNFS) and myxoinflammatory fibroblastic sarcoma (MIFS). Whether they represent neoplasms within the same tumor spectrum remains unclear. We performed a comparative clinicopathological, molecular, and epigenetic study of these two tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the clinicopathological features, immunophenotypes, and molecular profiles of three cases each of NNFS and MIFS. DNA methylation profiling was also performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All three NNFS cases were located in the trunk, presenting as well-circumscribed subcutaneous nodules with central necrosis, whereas the three MIFS cases all arose in acral sites with an infiltrative or ill-defined growth pattern. Morphologically, both NNFS and MIFS were characterized by large polygonal to epithelioid cells with virocyte-like, ganglion cell-like, or Reed–Sternberg-like appearance. Unlike MIFS, NNFS did not exhibit prominent myxoid stroma or vacuolated pseudolipoblasts. On immunohistochemistry, NNFS cases uniformly showed focal positivity for pancytokeratin (AE1/AE3), whereas MIFS cases exhibited variable CD34 expression. Molecular analysis identified <i>YAP1::MAML2</i> fusions in all three NNFS cases, while a <i>BRAF</i> rearrangement was detected in one of the three MIFS cases. DNA methylation profiling demonstrated that NNFS and MIFS cases clustered together forming a distinct group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although NNFS and MIFS each harbor unique genetic alterations, our DNA methylation profiling demonstrates a potential relationship between these two morphologically similar entities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 8","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652414","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":"Intramuscular Myoepithelioma-Like Hyalinizing Epithelioid Tumor With OGT::FOXO3 Intraexonic DNA Fusion Confirmed by Nanopore Sequencing","authors":"Naoki Takeda,&nbsp;Naohiro Makise,&nbsp;Hajime Kageyama,&nbsp;Mariko Oikawa,&nbsp;Yusuke Amano,&nbsp;Takahiro Sugiyama,&nbsp;Hideyuki Kinoshita,&nbsp;Yoko Hagiwara,&nbsp;Hiroto Kamoda,&nbsp;Tsukasa Yonemoto,&nbsp;Masahito Kawazu,&nbsp;Akinobu Araki","doi":"10.1002/gcc.70155","DOIUrl":"10.1002/gcc.70155","url":null,"abstract":"<div>\u0000 \u0000 <p>Myoepithelioma-like hyalinizing epithelioid tumor (MHET) is a rare mesenchymal neoplasm characterized by rearrangements of the <i>OGT</i> gene. MHET typically presents as a small tumor in the subcutis and generally follows a benign clinical course. Histologically, MHET is characterized by a hyalinized stroma exhibiting a distinctive “two-tone” appearance, epithelioid tumor cells with cellular processes encircling matrix globules, and a minor spindle cell component. The tumor also demonstrates rich vasculature with occasional fringe-like vessels, accompanied by perivascular concentric spindle cell proliferation and hyalinization. Nearly all documented <i>OGT</i> fusions in MHET are intraexonic; however, their precise genomic DNA breakpoints and the mechanisms underlying fusion transcript generation remain unclear. We report a case of MHET in a 17-year-old boy and investigate the genomic breakpoint of the fusion gene. Although the tumor showed atypical features, including large size, intramuscular location, and focal cytokeratin (CAM5.2) expression, the histologic findings were characteristic of MHET. Reverse transcription-polymerase chain reaction (RT-PCR) identified an intraexonic, in-frame <i>OGT::FOXO3</i> fusion transcript. To clarify the genomic breakpoint, nanopore DNA sequencing demonstrated that the DNA breakpoint was identical to the fusion junction in the mRNA transcript. These findings demonstrate that the fusion transcript was generated directly from rearranged genomic DNA without splice site involvement. This mechanism may contribute to the rarity of MHET and warrants further investigation.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584125","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":"TP53 Amplification, a Rare but Recurrent Alteration in Myeloid Neoplasms","authors":"Anna Stengel,&nbsp;Manja Meggendorfer,&nbsp;Torsten Haferlach,&nbsp;Wencke Walter","doi":"10.1002/gcc.70154","DOIUrl":"10.1002/gcc.70154","url":null,"abstract":"<div>\u0000 \u0000 <p>The tumor suppressor gene <i>TP53</i> is a key regulator of genomic stability, frequently altered across human cancers. In hematologic malignancies, <i>TP53</i> lesions—typically mutations, deletions, and copy-neutral loss of heterozygosity—are associated with complex karyotypes, therapy resistance, and dismal prognosis. Amplifications of <i>TP53</i>, however, have not been systematically described in this context. We retrospectively analyzed cases submitted to our laboratory (09/2005–10/2025) by interphase FISH in which we suspected a <i>TP53</i> amplification. Among these, eight cases exhibited <i>TP53</i> amplification, all classified as myeloid neoplasms (<i>n</i> = 6 acute myeloid leukemia, AML; <i>n</i> = 2 myelodysplastic neoplasms, MDS). Median patient age was 72 years (range 48–83). Chromosome banding revealed highly complex karyotypes in all cases (4–12 aberrations), including 5q deletions (in 7/8 patients) and −7/7q− (4/8). Targeted sequencing demonstrated concurrent <i>TP53</i> mutations in all patients (median variant allele frequency 48%, range 18%–91%) with few additional co-mutations. CNV (copy number variation) analysis confirmed focal <i>TP53</i> copy number gains, but whole-transcriptome sequencing showed only modest <i>TP53</i> expression increases, indicating that amplification did not translate into overexpression. Clinical data available for four AML cases revealed a median overall survival of 1 month. These findings indicate that <i>TP53</i> amplification, although rare, constitutes a recurrent event in myeloid neoplasms, uniformly accompanied by <i>TP53</i> mutation and complex cytogenetics. The combination of mutation and amplification likely confers biallelic <i>TP53</i> inactivation, aligning these cases with multi-hit <i>TP53</i> AML/MDS characterized by extreme genomic instability and highly adverse outcomes. Taken together, these data indicate that <i>TP53</i> copy number assessment may be of potential diagnostic interest, although its role in risk stratification requires further studies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535777","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":"Biphenotypic Sinonasal Sarcoma With a Novel PAX3::MAML2 Fusion","authors":"Mayu Uemura,&nbsp;Anna Fong Na Goh,&nbsp;Amit Kumar,&nbsp;Gary Quagliotto,&nbsp;Pranav Dorwal","doi":"10.1002/gcc.70153","DOIUrl":"10.1002/gcc.70153","url":null,"abstract":"<p>Biphenotypic sinonasal sarcoma (BSNS) is a rare, low-grade spindle cell sarcoma of the sinonasal tract. It is characterized by dual neural and myogenic differentiation and classically shows fusions involving <i>PAX3</i>. <i>MAML3</i>, a co-activator in the Notch signaling pathway, is the most common fusion partner of <i>PAX3</i>. Here, we describe the first reported case, to our knowledge, of BSNS harboring a novel <i>PAX3::MAML2</i> fusion in a polypoid lesion arising from the left ethmoid of a 61-year-old man. Microscopically, the tumor demonstrated bland spindle cell morphology. The cells were arranged in small fascicles and a vaguely whorled pattern without mitotic activity or cellular atypia. Immunohistochemistry displayed characteristic co-expression of S100 and smooth muscle actin as well as patchy nuclear positivity for beta-catenin. SOX10, AE1/AE3, EMA, and CD34 were negative. Ki-67 was expressed in less than 1% of tumor cells, consistent with a low-grade lesion. The RNA sequencing identified a novel <i>PAX3::MAML2</i> fusion transcript. <i>MAML2</i> fusion is commonly associated with other head and neck neoplasms, including mucoepidermoid carcinoma and <i>NR1D1</i>-rearranged tumors. These findings highlight the value of comprehensive fusion testing in BSNS and emphasize the evolving fusion landscape in this entity and related tumors.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375504","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 Affordable and Efficient In-House Approach for Detecting Gene Fusions in Bone and Soft Tissue Tumors Using a Custom Capture Panel and Nanopore Sequencing","authors":"Yoji Kukita,&nbsp;Ken-ichi Yoshida,&nbsp;Satoshi Takenaka,&nbsp;Keiichiro Honma,&nbsp;Toshinari Yagi","doi":"10.1002/gcc.70152","DOIUrl":"10.1002/gcc.70152","url":null,"abstract":"<div>\u0000 \u0000 <p>Accurate detection of gene fusions is critical for the diagnosis of bone and soft tissue tumors, yet conventional gene panel testing remains costly and impractical when processing small sample numbers. Here, we present a cost-effective and scalable in-house workflow using a custom capture panel combined with nanopore sequencing and TEQUILA-based probe synthesis. We analyzed 24 sarcoma samples with known gene fusions, comprising frozen and formalin-fixed paraffin-embedded (FFPE) specimens. Expected fusions were detected in all 7 frozen samples and in 16 of 17 FFPE samples. Long-read sequencing enabled direct characterization of full-length fusion transcripts, providing structural information beyond fusion junctions. Gene expression quantification showed strong concordance with short-read sequencing (Spearman <i>r</i> = 0.770–0.976), supporting quantitative reliability. Down-sampling analysis demonstrated that 100–200 Mb of sequencing data per sample was sufficient for reliable fusion detection, while deeper sequencing improved sensitivity for lowly expressed fusions. In addition, reuse of flow cells supported flexible and efficient sequencing for small sample batches. This approach provides a practical and extensible framework for in-house fusion detection and improves the accessibility of molecular diagnostics for rare cancers.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375471","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":"PKMYT1 in Cancer: Beyond Cell Cycle Checkpoints to Context-Dependent Therapeutic Vulnerability","authors":"Lingxi Li,&nbsp;Binfan He,&nbsp;Mengmeng Hao,&nbsp;Ye Liu,&nbsp;Shunxin Song,&nbsp;Rongzhang He","doi":"10.1002/gcc.70151","DOIUrl":"https://doi.org/10.1002/gcc.70151","url":null,"abstract":"<p>PKMYT1 has emerged as a promising therapeutic target distinguished by its tumor-selective expression and essential role in replication stress management. Unlike WEE1, PKMYT1 is dispensable in normal cell cycles but critical for cancer cells coping with DNA damage, establishing a broad therapeutic window. This vulnerability is exemplified by synthetic lethality in CCNE1-amplified and TP53-deficient contexts, where PKMYT1 inhibition triggers catastrophic mitotic entry. Beyond canonical cell cycle regulation, PKMYT1 functions as a multifaceted oncoprotein modulating signaling networks, metabolic reprogramming, and immune evasion via cGAS-STING activation. With selective inhibitors like lunresertib (RP-6306) now in Phase I/II trials, often combined with ATR inhibitors or chemotherapy, the field stands at a translational inflection point. However, context-dependent roles (e.g., tumor-suppressive functions in LUAD) and undefined resistance mechanisms pose challenges. This review critically evaluates PKMYT1's mechanistic underpinnings, clinical landscape, and biomarker strategies. We advocate for precision targeting based on genetic signatures (CCNE1, TP53, ER) to optimize therapeutic efficacy and overcome resistance in replication stress-high malignancies.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 7","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358024","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}