Genes, Chromosomes & Cancer最新文献

{"title":"A Novel Targeted Sequence for Chromosome 11p15.5 Maternal Loss in SDHD-Related Paragangliomas","authors":"Huei-Pin Lai,&nbsp;Chen-Hui Lee,&nbsp;Hsuan Hu,&nbsp;An-Ko Chung,&nbsp;Pei-Lung Chen,&nbsp;Wei-Shiung Yang,&nbsp;Wan-Chen Wu","doi":"10.1002/gcc.70107","DOIUrl":"https://doi.org/10.1002/gcc.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Hereditary paragangliomas (PGLs) caused by germline <i>SDHD</i> pathogenic variants (PVs) exhibit a parent-of-origin effect, with tumors arising almost exclusively when the PV is inherited from the paternal allele. The Hensen model proposes that a cluster of maternally expressed tumor suppressor genes (TSGs) on chromosome 11p15.5 may play a crucial role in <i>SDHD</i>-related PGL tumorigenesis, wherein somatic loss of maternal 11p and wild-type <i>SDHD</i> allele, in conjunction with a paternally inherited <i>SDHD</i> PV, triggers tumor development. To systematically localize and identify the most crucial maternal-expressed TSGs within 11p15.5, we developed a novel single nucleotide variant (SNV)-oriented, capture-based targeted enrichment approach followed by next-generation sequencing (NGS) to enable high-resolution loss-of-heterozygosity (LOH) analysis. Among 13 <i>SDHD</i>-related PGLs and 23 non-<i>SDHD</i>-related PGLs, a somatic loss of 11p15.5-15.4 was detected in 92% and 47%, respectively, a significant difference (<i>p</i> = 0.0035). Parental genotype analysis confirmed that the lost chromosome was of maternal origin. In our studies, 12/13 <i>SDHD</i>-related tumors demonstrated complete loss of the maternal 11p15.5-15.4 region, preventing localization of a specific driver TSG. Only one exceptional <i>SDHD</i>-related tumor retained this region, warranting further investigation into the mechanism underlying parent-of-origin tumorigenesis.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146007740","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":"GLI1-Altered Mesenchymal Tumor of the Duodenum With a Novel TNFAIP3::GLI1 Gene Fusion: Report of a Diagnostically Challenging Case Associated With Late Metastasis","authors":"Pedram Argani,&nbsp;He Fang,&nbsp;Yajuan J. Liu,&nbsp;Ezra Baraban,&nbsp;John M. Gross","doi":"10.1002/gcc.70104","DOIUrl":"10.1002/gcc.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>We report a <i>GLI1</i>-altered mesenchymal tumor of the duodenum with a novel <i>TNFAIP3::GLI1</i> gene fusion, deceptive morphology, and late recurrence. The patient was a 72-year-old female who was found to have a polypoid 3.7 cm duodenal mass which, based on epithelioid morphology and focal immunoreactivity for cytokeratin, was diagnosed as invasive adenocarcinoma following review by an academic consultant. Sixty-seven months later, the patient presented with multiple liver nodules representing metastatic disease. RNA sequencing demonstrated a novel <i>TNFAIP3::GLI1</i> gene fusion in the liver lesion, which had higher mitotic activity but showed similar pure epithelioid morphology and immunophenotype as the original small bowel lesion. In addition to expanding the spectrum of <i>GLI1</i>-associated gene fusions, this case highlights the potential for misdiagnosis of epithelioid <i>GLI1</i>-altered mesenchymal tumors as adenocarcinoma (particularly given the variable immunoreactivity for cytokeratin), and the need for long-term follow up of these typically slowly growing neoplasms.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849917","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":"Spatial Dynamics of Tumor Cell Plasticity in Lung Adenocarcinoma Revealed by Region-Specific Single Cell Transcriptomics","authors":"Anna A. Khozyainova,&nbsp;Maxim E. Menyailo,&nbsp;Vera G. Subrakova,&nbsp;Dmitry M. Loos,&nbsp;Pavel S. Iamshchikov,&nbsp;Anton A. Fedorov,&nbsp;Maria S. Tretyakova,&nbsp;Ustinia A. Bokova,&nbsp;Evgeny O. Rodionov,&nbsp;Sergey V. Miller,&nbsp;Evgeny B. Topolnitsky,&nbsp;Denis V. Piankov,&nbsp;Sergei A. Korostelev,&nbsp;Evgeny V. Denisov","doi":"10.1002/gcc.70101","DOIUrl":"10.1002/gcc.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumor cell plasticity plays a key role in the progression of malignant neoplasms and therapy resistance, yet its spatial dynamics remain poorly understood. This study investigates the spatial distribution of epithelial–mesenchymal transition (EMT) and stemness, and their prognostic relevance in lung adenocarcinoma (LUAD). Single-cell RNA sequencing was performed on 10 tumor fragments from three regions (core, core-adjacent, and edge) of a single LUAD using a SURFSeq 5000 platform. Stemness potential was identified by CytoTRACE2, EMT by UCell and the Hallmark_epithelial_mesenchymal_transition signature, and tumor cells associated with disease prognosis by Scissor. LUAD displayed pronounced spatial heterogeneity of tumor cell plasticity. Stemness potential was heightened at the edge, while EMT was most prominent in the core. The correlation between EMT and stemness was slightly higher at the edge, though it remained negligible (<i>R</i> = 0.17, <i>p</i> = 5.5e⁻⁷). Higher EMT scores were observed in tumor cells associated with poor overall survival (<i>r</i> = 0.433, <i>p</i> &lt; 2e⁻¹⁶), whereas stemness was prevalent in tumor cells associated with poor progression-free survival (<i>r</i> = 0.251, <i>p</i> = 7.15e⁻⁶). Tumor cells associated with poor prognosis were enriched with the MYC-targets v1 signature with <i>PCBP1</i> and <i>PA2G4</i> as the top contributing genes. Immunohistochemical data showed that PCBP1 and PA2G4 proteins predominantly localized within tumor cells of LUAD. Taken together, these findings highlight the spatial heterogeneity of tumor cell plasticity features in LUAD and uncover biomarkers associated with poor prognosis.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843544","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 Role of RB1 and Secondary Genomic Changes in the Development of Spindle Cell and Pleomorphic Lipomas","authors":"Maria Hellberg,&nbsp;Valeria Difilippo,&nbsp;Emilia Gottberg,&nbsp;Asle Hesla,&nbsp;Felix Haglund de Flon,&nbsp;Jenny Nilsson,&nbsp;Linda Magnusson,&nbsp;Saskia Sydow,&nbsp;Paul Piccinelli,&nbsp;Jakob Hofvander,&nbsp;Fredrik Mertens","doi":"10.1002/gcc.70102","DOIUrl":"10.1002/gcc.70102","url":null,"abstract":"<p>Spindle cell lipomas (SCL) and pleomorphic lipomas (PL) are today considered a single tumor entity (SCLPL). Atypical SCLPL, in contrast, represents a recently recognized related but distinct entity. Here we explored the correlation between genomic features and morphological aspects of SCLPL and atypical SCLPL and the role of the <i>RB1</i> gene in tumor development. Seventy-one samples from 68 patients with SCLPL or atypical SCLPL, as well as a lipomatous tumor from a retinoblastoma patient with a germline pathogenic variant in the <i>RB1</i> gene, and two pleomorphic liposarcomas were analyzed using chromosome banding, high-resolution genomic arrays (SNP array), whole exome sequencing (WES), and/or RNA sequencing (RNA-seq). Common for all tumors was involvement of 13q; other recurring variants were deletion of 16q, 6q, and 17p. A minimally deleted region that only contained <i>RB1</i> was found on 13q. A distinction was seen between SCL on the one hand and PL and atypical SCLPL on the other; SCL had fewer copy number aberrations in general, and loss of 17p/<i>TP53</i> gene or a SNV affecting <i>TP53</i> was only rarely detected in SCL but seen in the vast majority of PL and atypical SCLPL tumors. Thus, at the molecular level, SCL is different from PL/atypical SCLPL. Furthermore, the finding of the same copy number changes (loss of 13q, 6q, 16q, and 17p) in some pleomorphic liposarcomas raises the possibility that a subset of SCLPL/atypical SCLPL have the potential for malignant transformation.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809465","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":"Clinical and Pathologic Description of Three Aneurysmal Bone Cyst Cases With Novel USP6 Fusion Partners Including SEC24D, HNRNPC, and ERRFI1","authors":"Patrick R. Blackburn,&nbsp;Zonggao Shi,&nbsp;Maria F. Cardenas,&nbsp;Mark R. Wilkinson,&nbsp;Robert E. Ruiz,&nbsp;Teresa Santiago,&nbsp;Paul H. Yi,&nbsp;Mohammad K. Eldomery,&nbsp;Faizan Malik","doi":"10.1002/gcc.70103","DOIUrl":"10.1002/gcc.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>Ubiquitin-specific protease 6 (USP6)-associated neoplasms constitute a spectrum of related entities that share clinical and morphological characteristics. They are defined molecularly by the presence of a <i>USP6</i> gene rearrangement that results in promoter swap fusions involving a range of partner genes that activate expression of full-length <i>USP6</i>. In this study, we retrospectively reviewed whole transcriptome results and identified <i>USP6</i>-associated neoplasms in the St. Jude clinical genomics cohort, with a focus on novel fusion partners. Three patients (ages 4–21 years) presented with bone lesions affecting the humerus, femur, and distal femur, respectively. Histological examination revealed characteristic aneurysmal bone cyst (ABC) features including cystic spaces, osteoclastic giant cells with smooth muscle actin positivity in myofibroblastic cells, and at least one case with prominent myxoid features. Clinical whole transcriptome RNA sequencing identified three previously unreported <i>USP6</i> fusions including <i>SEC24D</i>::<i>USP6</i>, <i>HNRNPC</i>::<i>USP6</i>, and <i>ERRFI1</i>::<i>USP6</i>. All fusions resulted in transcriptional upregulation of <i>USP6</i>. In this report, we summarize the clinical, radiographic, and histologic presentations of these new cases and describe the associated fusion structures.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809342","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":"Expanding the Morphologic and Molecular Spectrum of Spindle Cell Tumors Associated With TERT Fusions","authors":"Susan Swee-Shan Hue,&nbsp;Carla Saoud,&nbsp;Dorukhan Bahceci,&nbsp;Liliana Villafania,&nbsp;Jamal Benhamida,&nbsp;Cristina R. Antonescu","doi":"10.1002/gcc.70097","DOIUrl":"https://doi.org/10.1002/gcc.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>The incidence and impact of telomerase reverse transcriptase (TERT) gene fusions in sarcomas remain poorly defined. To date only two cases have been reported, both displaying spindle cell liposarcoma morphology. In this study, we identified four soft tissue spindle cell neoplasms harboring in-frame TERT fusions using targeted RNA sequencing and provide an in-depth characterization of their histologic spectrum, immunoprofile and genomic landscape. Clinically, there was one female and three males, with a wide age range at diagnosis (47–79 years, mean 60 years). The tumors showed a diverse anatomic location, including lower extremity, trunk and retroperitoneum. Histologically, they exhibited a predominantly monomorphic spindle cell phenotype, in keeping with fibroblastic/myofibroblastic differentiation. Three tumors were low-grade, while one displayed increased cellularity and mitotic activity in keeping with a high-grade lesion. Two tumors showed CD34 positivity, while the other two were characterized by actin positivity, with one showing nuclear β-catenin expression. All cases harbored in-frame <i>TERT</i> fusions, involving three different partners, such as <i>TRIO</i> in two cases, and <i>AHRR</i> and <i>SUGCT</i> in one case each. Two of the three cases tested by targeted NGS panels showed in addition <i>TERT</i> gene amplification and <i>CDKN2A</i> deletion, including the high-grade lesion. To define more broadly the recurrent potential and histotype distribution of <i>TERT</i> fusions we also investigated our sarcoma genomic database for this genetic alteration. Results showed that a small subset of well-defined sarcoma types harbored <i>TERT</i> fusions, typically coexisting with numerous other genomic alterations. Thus, our findings suggest that in-frame <i>TERT</i> fusions may drive the pathogenesis of a group of mostly low-grade unclassified sarcomas with fibroblastic/myofibroblastic differentiation. In contrast, <i>TERT</i> fusions may also be detected in other common sarcoma types co-occurring with numerous genomic alterations, likely representing a secondary driver event.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 12","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739751","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":"NF1 Mutated Gastrointestinal Stromal Tumors With Coamplification of MDM2 and MYC","authors":"Xinyang Chen,&nbsp;Yang Lu,&nbsp;Xin He,&nbsp;Du He,&nbsp;Min Chen,&nbsp;Hongying Zhang","doi":"10.1002/gcc.70096","DOIUrl":"10.1002/gcc.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>We report a unique case of a 57-year-old man with a gastrointestinal stromal tumor (GIST) that developed a high-grade phenotype and additional genetic alterations in the subsequent recurrence. Histologically, the initial resected tumor showed a typical morphology with uniform spindle-shaped cells arranged in fascicular and whorling patterns. However, based on large tumor size and mitotic activity it was designated as high risk. Tumor cells were immunoreactive for CD117 and DOG1. Mutational analysis identified no <i>KIT</i> or <i>PDGFRA</i> hotspot mutations. Next-generation sequencing (NGS) further demonstrated an <i>NF1</i> mutation (c.1466A&gt;G) without <i>KIT</i> or <i>PDGFRA</i> mutations. In contrast, the recurrent tumor displayed a higher-grade morphology. Tumor cells were positive for MDM2, while showing decreased expression for CD117 and DOG1. NGS and molecular assays detected no <i>KIT</i> or <i>PDGFRA</i> mutations, but confirmed the <i>NF1</i> mutation (c.1466A&gt;G). In addition, NGS identified <i>MDM2</i> and <i>MYC</i> amplification. This is the first report describing an <i>NF1</i>-mutant GIST harboring coamplification of <i>MDM2</i> and <i>MYC</i> and associated with a higher-grade tumor progression.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603715","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 Resistance Mechanisms to Second-Generation EGFR Tyrosine Kinase Inhibitor Afatinib and Associations With Genomic Features in NSCLC","authors":"Fengwu Lin,&nbsp;Miaoqing Zhao,&nbsp;Qiang Wu,&nbsp;Wenqi Wu,&nbsp;Xiaoying Wu,&nbsp;Ya Ma,&nbsp;Jiani C. Yin,&nbsp;Meng Yang,&nbsp;Min Gao","doi":"10.1002/gcc.70088","DOIUrl":"https://doi.org/10.1002/gcc.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Afatinib, an irreversible pan-ERBB family inhibitor, has demonstrated promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon <i>EGFR</i> activating mutations. However, besides the acquisition of the secondary T790M mutation, other resistance mechanisms to afatinib remain to be explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This study retrospectively included 37 NSCLC patients harboring either <i>EGFR</i> or <i>ERBB2</i> activating mutations, who had received afatinib as first-line treatment. Targeted next-generation sequencing data on the baseline and post-progression samples were subjected to analysis. Comparative analyses of clinical parameters and genomic features were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, the progression-free survival of the <i>EGFR</i>-mutated patients on first-line afatinib was longer than that of the <i>ERBB2</i>-positive patients (hazard ratio = 0.35 [95% confidence interval = 0.15–0.79], <i>p</i> = 0.008). Primary resistance was associated with the presence of exon 20 insertion mutation (<i>p</i> = 0.011), higher tumor mutational burden (<i>p</i> = 0.009), and higher proportion of APOBEC signature (<i>p</i> = 0.012), which were all enriched in the <i>ERBB2</i>-mutated cohort. We further characterized acquired resistance to afatinib and discovered that baseline <i>EGFR</i> exon 19 deletions and higher levels of chromosomal instability and age-related mutational signatures would contribute to the development of known resistance mechanisms such as <i>EGFR</i> T790M or <i>MET</i> amplification. We also report gaining <i>EGFR</i> activating mutations and losing <i>CDKN2A</i>, <i>NF1</i>, or the original <i>ERBB2</i> mutations as novel resistance mechanisms to afatinib for <i>ERBB2</i>-mutated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study identified multiple genomic characteristics associated with primary and secondary resistance to first-line afatinib treatment in <i>EGFR</i>- and <i>ERBB2</i>-positive subpopulations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572591","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":"“Benign” Metastasizing Fibrous Histiocytoma Harboring PRKCD Gene Fusions With Malignant Clinical Course","authors":"Charlotte I. Wang,&nbsp;Anne B. Giersch,&nbsp;Santiago Lozano Calderon,&nbsp;Edwin Choy,&nbsp;Fantine N. Giap,&nbsp;Yin P. Hung,&nbsp;G. Petur Nielsen,&nbsp;Ivan Chebib","doi":"10.1002/gcc.70094","DOIUrl":"10.1002/gcc.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Dermatofibroma/fibrous histiocytoma is a common tumor of the dermis, composed of myofibroblasts, dendrocytes, and macrophages with characteristic entrapment of dermal collagen fibers at the periphery of the tumor. Various subtypes of dermatofibroma, including cellular, aneurysmal, and atypical dermatofibroma, are associated with an increased risk of recurrence, especially with incomplete excision. Two cases of benign fibrous histiocytoma with recurrence and metastasis are described. Patient 1 had a cellular fibrous histiocytoma with <i>KIRREL1</i>::<i>PRKCD</i> fusion presenting as a superficial and deep soft tissue mass involving the scapula and lateral clavicle. Patient 1 subsequently developed metastasis to the chest wall and thigh. Patient 2 had a recurrent aneurysmal fibrous histiocytoma with <i>LAMTOR1</i>::<i>PRKCD</i> fusion presenting as a large shoulder mass with invasion of the clavicle and lymph node metastasis. Patient 2 developed rapid local recurrence and PET-avid pulmonary nodules, radiologically consistent with metastasis. Fibrous histiocytoma is typically a morphologically benign neoplasm that only rarely exhibits clinically aggressive behavior with multiple recurrences and metastases. Although uncommon, recognition of this entity is important so that pathologists and sarcoma oncologists can ensure accurate diagnosis, multidisciplinary management, and appropriate clinical surveillance. In addition, complex chromosomal abnormalities may serve as useful indicators of fibrous histiocytoma with the risk of aggressive clinical behavior.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549177","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":"A 107 Gene Nanostring Assay Effectively Translates the Cancer Genome Atlas, and Tumour Microenvironment Gastric Cancer Molecular Classification to a Patient-Derived Organoid Model","authors":"D. Skubleny,&nbsp;K. Purich,&nbsp;T. Williams,&nbsp;D. R. McLean,&nbsp;S. N. Martins-Filho,&nbsp;K. Buttenschoen,&nbsp;E. Haase,&nbsp;M. McCall,&nbsp;K. Baker,&nbsp;S. Ghosh,&nbsp;J. L. Spratlin,&nbsp;D. E. Schiller,&nbsp;G. R. Rayat","doi":"10.1002/gcc.70090","DOIUrl":"10.1002/gcc.70090","url":null,"abstract":"<p>There is a need to improve the translation of gastric cancer molecular classification schemes, such as those proposed by the Cancer Genome Atlas (TCGA) and Tumour Microenvironment score (TME), to clinical specimens and three-dimensional organoid culture models. In this study, we validate a 107-gene Nanostring assay informed by previously established machine learning models using a prospective cohort of gastric adenocarcinoma tumours and tumour-organoid pairs. Thirty-eight gastric adenocarcinoma specimens and twelve parent tumour-tumour organoid pairs were assigned TCGA and TME subtypes using gene expression measured by our custom Nanostring gene set. Subtypes were validated using gold-standard tests for Epstein–Barr virus (EBV) and microsatellite instability (MSI). Molecular subtype scores were compared to known clinicopathologic characteristics. The correlation between dose–response and molecular subtypes using an organoid drug assay and the Cancer Cell Line Encyclopedia (CCLE) was investigated. TCGA and TME subtypes were successfully applied to all specimens. The relationship of molecular subtype scores in our population compared to public cohorts was statistically identical for Lauren Class and Signet Ring status. Our method achieved 100% accuracy in labeling EBV and MSI subtypes. We identified 81.8% and 63.6% concordance between parent tumour-tumour organoid pairs for TME and TCGA subtypes, respectively. No significant correlation was identified between dose response to chemotherapy and molecular subtype scores. Analysis of the CCLE identified promising personalized therapy candidates for each molecular subtype. Our 107-gene Nanostring test successfully assigns TCGA and TME molecular subtypes to clinical tumour and tumour organoid samples for use in future study.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12612569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503447","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}