Genes, Chromosomes & Cancer最新文献

{"title":"Causative Role for a BRCA2 Germline Pathogenic Variant in External Auditory Canal Squamous Cell Carcinoma","authors":"José Camacho-Valenzuela,&nbsp;Dylan Pelletier,&nbsp;Paz Polak,&nbsp;Lili Fu,&nbsp;Nancy Hamel,&nbsp;Carla Daniela Robles-Espinoza,&nbsp;William D. Foulkes","doi":"10.1002/gcc.70123","DOIUrl":"10.1002/gcc.70123","url":null,"abstract":"<p>External auditory canal squamous cell carcinoma (EACSCC) is rare, affecting 1.6 in a million individuals. We report a case of EACSCC in a 66-year-old woman carrying a heterozygous <i>BRCA2</i> germline pathogenic variant (GPV) (c.8537_8538del), with prior history of breast cancer. Tumor copy-number analysis showed loss of heterozygosity at the <i>BRCA2</i> locus. Genomic scar analysis supported homologous recombination repair deficiency (HRD), with mutational signatures showing the predominance of APOBEC activity and lower contributions of HRD-associated single base (SBS3, SBS8) and INDEL (ID6) signatures. A somatic <i>TP53</i> pathogenic variant was also identified. These findings suggest a contributory role for <i>BRCA2</i> in EACSCC development.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638580","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":"Sibling Osteosarcoma Without Retinoblastoma Associated With a Low Penetrance RB1 Variant: Whole Genome Findings From a Single Family","authors":"Weisong Zhao,&nbsp;Zhuoying Wang,&nbsp;Kai Tian,&nbsp;Xiyu Yang,&nbsp;Yafei Jiang,&nbsp;Zhiwei Cheng,&nbsp;Wei Sun,&nbsp;Gangyang Wang,&nbsp;Zhengdong Cai,&nbsp;Yingqi Hua","doi":"10.1002/gcc.70124","DOIUrl":"10.1002/gcc.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, yet its genetic etiology remains poorly understood. In this study, we described a family from the Shanghai General Hospital Osteosarcoma (SGH-OS) cohort in which two siblings developed osteosarcoma as their first primary malignancy, and we investigated the germline and somatic genetic basis underlying this familial presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-genome sequencing (WGS) was performed on tumors and matched germline DNA from the affected siblings, as well as germline DNA from their parents and unaffected sister. Comprehensive somatic and germline analyses were conducted to assess mutational profiles, copy-number alterations, and structural variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both affected siblings carried a paternally inherited RB1 splice-donor variant (NM_000321.3:c.539+1G&gt;A), with biallelic inactivation confirmed by 13q14 loss in both tumors. Tumor WGS revealed additional somatic alterations, suggesting cooperation between germline and acquired mutations in osteosarcoma development. In addition, the carrier father and elder sister remained unaffected, consistent with incomplete penetrance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study further supports the expanding spectrum of RB1-associated cancer predisposition, showing that low-penetrance RB1 variants may present with osteosarcoma without preceding retinoblastoma. In addition, our findings underscore the value of integrated WGS for characterizing inherited susceptibility in familial osteosarcoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633142","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":"Multimodal Cytogenetic and Molecular Approach for the Detection of a Constitutional Balanced Paracentric Inversion Disrupting RB1 in an Infant With Bilateral Retinoblastoma","authors":"Arti S. Pandey,&nbsp;Alexa Siskar,&nbsp;Alice Moore,&nbsp;Kim E. Nichols,&nbsp;Julieann C. Lee,&nbsp;Matthew W. Wilson,&nbsp;Mohammad K. Eldomery,&nbsp;Jie Liu,&nbsp;Patrick R. Blackburn","doi":"10.1002/gcc.70120","DOIUrl":"10.1002/gcc.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>We report a case of hereditary bilateral retinoblastoma due to a <i>de novo</i> germline inversion on chromosome 13, resulting in disruption of the <i>RB1</i> gene. The patient is a 22-month-old female who initially presented to the emergency room at 11 months of age with an erythematous left eye and leukocoria of the right eye. Computed tomography (CT) of the brain and orbits showed solid internal calcifications arising from the posterior globes concerning for bilateral retinoblastoma. Magnetic resonance imaging (MRI) of the brain and orbits confirmed bilateral retinoblastoma without associated pineal region or suprasellar mass. On initial examination under anesthesia, the right eye showed one tumor in the macula and two tumors in the inferior mid-periphery. Sub-retinal seeding extended to the inferior periphery. The left eye was enucleated and pathology showed leptomeningeal extension along the optic nerve extending to the surgical margin. The patient was treated on a non-protocol treatment plan with five cycles of vincristine, carboplatin, etoposide, cyclophosphamide, and weekly intraventricular topotecan via Ommaya reservoir, followed by autologous stem cell rescue. Tumor analysis showed loss of pRB protein expression by immunohistochemistry and methylation copy number profiling showed several segmental gains and losses, including focal loss of <i>RB1</i> on 13q. A 123-gene cancer predisposition germline panel using genome and exome sequencing initially did not identify any <i>RB1</i> single nucleotide variants or insertion/deletions. Subsequent constitutional chromosome analysis for <i>RB1</i> showed a paracentric inversion between bands 13q14.2 and 13q31. Optical genome mapping (OGM) showed that the proximal breakpoint of the balanced inversion at 13q14.2 was within intron 17 of <i>RB1</i>, while the distal breakpoint at 13q31.3 did not interrupt any known genes of clinical significance. We review the various molecular techniques that aided in diagnosis of this patient and provide a summary of similar <i>RB1</i>-disrupting structural variants reported in the literature.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147622565","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":"CRTC1::TRIM11 Cutaneous Tumors With Atypia: Melanoma Mimicry, Aggressive Potential, and Methylation Classifier Limitations.","authors":"Bethany Batson, Arivarasan Karunamurthy, Azfar Neyaz, John M Skaugen, Steven D Billings, Karen Fritchie, Ivy John","doi":"10.1002/gcc.70127","DOIUrl":"10.1002/gcc.70127","url":null,"abstract":"<p><p>CRTC1::TRIM11 cutaneous tumors are an emerging subset of MITF pathway-activated neoplasms that typically present as dermal nodules and can closely mimic clear cell sarcoma or malignant melanoma. Most reported tumors behave in an indolent manner, yet rare malignant cases have been documented. We report three additional CRTC1::TRIM11 cutaneous tumors with atypical features, including two patients with nodal or visceral disease at presentation. Histologically, all three tumors showed marked cytologic atypia with prominent nucleoli, and the usual nested and short-fascicular architecture was largely replaced by broad sheet-like growth, raising concern for melanoma. The tumors expressed SOX10 (diffuse) and S100 protein (patchy) with focal to absent expression of Melan-A and HMB45. PRAME was negative. CRTC1::TRIM11 was confirmed in all tumors. Two tumors harbored TERT promoter mutations, and one showed additional low-level copy-number gains of 1q, 8q, and 12q with 14q loss. In one case, methylation profiling yielded a clear cell sarcoma score of 0.885, just below the confidence threshold, likely due to shared CREB-MITF pathway activation and the lack of a dedicated CRTC1::TRIM11 reference class. A literature review identified nine previously reported metastatic CRTC1::TRIM11 cutaneous tumors. When combined with our series, extremities were the predominant primary site, and metastases most often involved regional lymph nodes and the lung. Fusion status remains the molecular gold standard, while secondary events such as TERT promoter mutations and 8q gains may contribute to aggressive behavior in a subset of tumors.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":"e70127"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769239","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":"Transcript-Specific DNA Methylation Alterations of the RASSF1 Locus in Cancer Cells.","authors":"Litzy Gisella Bermudez, Camila Bernal Forigua, Carmen María Ayala-Roldán, Jesús Manuel Romero, Rafael R Ariza, Teresa Morales-Ruiz, Teresa Roldán-Arjona, Alejandra Cañas, Adriana Rojas","doi":"10.1002/gcc.70125","DOIUrl":"10.1002/gcc.70125","url":null,"abstract":"<p><strong>Background: </strong>The locus encoding Ras association domain family member 1 (RASSF1) encodes multiple transcripts with opposing roles in cancer, such as RASSF1A (tumor suppressor), RASSF1C (oncogene), and the lncRNA RASSF1-AS1 (function undefined). Although DNA methylation-mediated repression of RASSF1A expression has been extensively studied in different cancer types, the epigenetic regulation of RASSF1C and RASSF1-AS1 is unclear. We profiled gene expression and promoter DNA methylation of RASSF1A, RASSF1C, and RASSF1-AS1 across 11 tumor cell lines, quantified RASSF1A methylation in lung cancer tissues and plasma by quantitative methylation-specific PCR (qMSP), and integrated single-CpG methylation (pyrosequencing) with in silico transcription factor binding site (TFBS) prediction.</p><p><strong>Results: </strong>We found that RASSF1A promoter hypermethylation was strongly and inversely associated with its mRNA levels. In contrast, RASSF1C promoter methylation did not correlate with expression. RASSF1-AS1 showed low promoter methylation accompanied by high expression. In clinical samples, RASSF1A methylation was detected in tissue biopsy (54% of cases) and plasma (42% of cases) from lung cancer patients, whereas no methylation was detected in 85% of control individuals, regardless of their smoking history. Finally, the analysis of DNA methylation at specific CpG sites combined with the prediction of TFBS in the evaluated promoter regions allowed the identification of binding domains overlapping differentially methylated regions. Notably, the RASSF1C promoter region exhibited a higher TFBS frequency containing CpG sites with low methylation levels, as determined by pyrosequencing.</p><p><strong>Conclusions: </strong>These findings highlight isoform-specific epigenetic regulation at the RASSF1 locus and suggest that RASSF1A methylation may represent a promising minimally invasive marker in lung cancer.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":"e70125"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728567","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":"Spindle Cell Rhabdomyosarcoma of Oral Cavity With TCF12::VGLL3 Fusion, Expanding on a Recently Described Entity With Digital Spatial Profiling and Long-Term Follow Up.","authors":"Nooshin K Dashti, Debopriya Chakraborty, Madhumala K Sadanandappa, Carina A Dehner, Paul J Zhang, Joseph A Paydarfar, Laura J Tafe","doi":"10.1002/gcc.70126","DOIUrl":"10.1002/gcc.70126","url":null,"abstract":"<p><p>Recently, a distinct, bland spindle cell neoplasm with rhabdomyoblastic phenotype, and VGLL3 rearrangement has been described. These tumors have a striking predilection for the head and neck area and so far, followed an indolent course. It remains unclear whether these tumors are best classified as true rhabdomyosarcomas. There are 11 reports of such tumors with limited follow-up. Here, we report an additional case with local recurrence, long-term follow-up and spatial profiling. The tumor occurred in the right buccal mucosa/oral commissure of a 47-year-old man. On clinical examination, the mass was firm, measuring ~1.5 cm. Biopsy and subsequent wedge excision were performed. Histologically, the tumor was composed of bland, small, spindle to ovoid cells, arranged in short fascicles and vaguely storiform architecture. The tumor cells diffusely infiltrated into skeletal muscle. There was a background of inflammatory cells including small lymphocytes and histiocytes. Neoplastic cells were positive for SMA, demsin, PAX7, myogenin and MyoD1. Whole transcriptome sequencing revealed a TCF12::VGLL3 fusion. Digital spatial profiling (DSP) identified pan-AKT expression, differential expression in the MAPK pathway, and revealed that the tumor attracted a dense T-cell rich inflammatory infiltrate. The patient had a lesion in the same location 6 years prior that underwent incisional biopsy, showed intense inflammatory infiltrate, and was interpreted as benign. FISH for VGLL3 on this tissue was positive for rearrangement. No additional adjuvant treatment was given, and the patient is alive without disease, 8 months after the major resection. Long term follow-up of 6 years with only local recurrence lends further support to the notion that these neoplasms are a class of indolent/low-grade rhabdomyoblastic tumors that are biologically and clinically distinct from fully malignant spindle cell rhabdomyosarcomas.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 4","pages":"e70126"},"PeriodicalIF":2.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689825","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":"Myeloid Neoplasms With a t(5;12)(q31;p13) and an Associated ETV6::ACSL6 Gene Fusion Are Diagnostically Challenging and Have a Poor Prognosis","authors":"Bettina Balk,&nbsp;Marietta Truger,&nbsp;Wencke Walter,&nbsp;Alexander Schauwvlieghe,&nbsp;Johannes Lübke,&nbsp;Torsten Haferlach,&nbsp;Claudia Haferlach,&nbsp;Andreas Reiter,&nbsp;Anna Stengel","doi":"10.1002/gcc.70119","DOIUrl":"10.1002/gcc.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>ETV6</i>::<i>ACSL6</i> fusion gene resulting from the reciprocal translocation t(5;12)(q31;p13) is a rare but recurrent aberration in patients with myeloid neoplasms of variable phenotype. Cytogenetically, there is a high resemblance to the t(5;12)(q32;p13) leading to the imatinib-sensitive <i>ETV6</i>::<i>PDGFRB</i> fusion gene. Therefore, distinction of these entities by complementary molecular genetic tools is crucial, as patients with <i>ETV6</i>::<i>ACSL6</i> fusion have a poor prognosis with no response to imatinib or alternative tyrosine kinase inhibitors (TKI). We performed a comprehensive analysis of 7 patients harboring the <i>ETV6</i>::<i>ACSL6</i> fusion, using clinical and morphological characteristics, chromosome banding analysis (CBA), fluorescence in situ hybridization (FISH) and molecular genetic analyses including whole transcriptome sequencing (WTS) as well as whole genome sequencing (WGS). Patients presented with an increase in leukocytes, eosinophils and basophils. The phenotype was a chronic myeloid neoplasm in 6 patients and acute myeloid leukemia (AML) in 1 patient. The t(5;12)(q31;p13) was the sole abnormality in four out of seven cases, and the remaining 3 cases showed a complex karyotype with ≥ 3 aberrations comprising a <i>TP53</i> deletion. No recurrent molecular mutations or other fusions were identified, suggesting that <i>ETV6</i>::<i>ACSL6</i> functions as a driver event in the pathogenesis of all cases. Five out of seven patients received intensive chemotherapy, including allogeneic hematopoietic transplantation (alloHCT) in 4 patients. The median overall survival of 5 patients with available follow-up was 11 months. We conclude that the reciprocal translocation t(5;12)(q32;p13) requires a careful and step-wise diagnostic work-up to differentiate between an underlying <i>ETV6::PDGFRB</i> fusion gene with associated excellent prognosis on imatinib and an <i>ETV6::ACSL6</i> fusion gene, for which the prognosis is poor and alloHCT appears to be a promising therapeutic option.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive RNA Sequencing Analysis Reveals Heterogeneous Expression of Epstein–Barr Virus Genes in Gastric Cancer","authors":"Yasuko Fujita,&nbsp;Katsuhiro Masago,&nbsp;Eiichi Sasaki,&nbsp;Shiro Fujita,&nbsp;Katsutoshi Seto,&nbsp;Hiroaki Kuroda,&nbsp;Yoshitsugu Horio,&nbsp;Hirokazu Matsushita","doi":"10.1002/gcc.70117","DOIUrl":"10.1002/gcc.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>Epstein–Barr virus-associated gastric cancer (EBVaGC) is a distinct histological and molecular subtype of gastric cancer. Histologically, it is characterized by marked lymphocytic infiltration; molecularly, it exhibits a hypermethylated phenotype. The diagnosis of surgical pathology relies on the detection of BEV-encoded RNA in situ hybridization (EBER-ISH) in tumor cells. To diagnose the histological type related to EBV is crucial, as EBVaGC is a potential target for treatment with programed cell death-1/programed cell death ligand-1 inhibitors. This study comprehensively analyzed viral and tumor gene expression in EBVaGC using RNA sequencing (RNA-seq). Six cases of EBVaGC, including one with heterogeneous EBER-ISH expression, were investigated. RNA was extracted from formalin-fixed, paraffin-embedded tissue sections and analyzed using RNA-seq. EBER-ISH-positive and negative areas from tumors with heterogeneous EBER-ISH expression were separately collected using modified manual microdissection techniques. EBV gene expression in EBVaGCs varied among the tumors. Viral gene expression was observed even in EBER-ISH-negative lesions in tumors showing heterogeneous EBER-ISH expression. Gene expression and set enrichment analyses revealed that EBVaGC was highly immunogenic, whereas EBER-ISH-negative lesions were not. However, EBVaGC tumor gene expression patterns, including EBER-ISH-negative lesions, were classified into the same cluster. Viral RNA expression in EBVaGC was heterogenous and even <i>EBER</i> expression fluctuates, suggesting that EBV infection in EBVaGC may not be detected by EBER-ISH alone.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456657","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":"TRAF7-Mutated Fibromyxoid Spindle Cell Tumor of Bone: An Osseous Case Expanding the Spectrum of TRAF7-Mutated Tumors With Over 20 Years Clinical Follow-Up","authors":"Laura M. Warmke,&nbsp;Ani Toklu,&nbsp;Spencer M. Richardson,&nbsp;Christopher D. Collier,&nbsp;L. Daniel Wurtz,&nbsp;Lauren M. Ladd,&nbsp;Roman Shrestha,&nbsp;Devin J. Conway","doi":"10.1002/gcc.70118","DOIUrl":"10.1002/gcc.70118","url":null,"abstract":"<p><i>TRAF7</i> mutations are a rare occurrence in human cancer and have recently been described in a group of mesenchymal tumors with varying clinical course. Herein, we expand the spectrum of <i>TRAF7</i>-mutated fibromyxoid spindle cell tumors by reporting the first case to arise in bone. A 60-year-old woman presented with right knee pain and was incidentally found to have a left distal femur lesion, which was first detected 20 years prior when it was favored to be benign. Recent imaging studies revealed significant interval growth with focal cortical destruction and soft tissue extension. Histologic examination showed a bland spindle cell neoplasm with fibrous to myxoid stroma. Rare mitotic figures were present; necrosis and marked cytologic atypia were absent. Immunohistochemical work-up showed that the spindle cells only demonstrated focal cytoplasmic staining with L1CAM, and whole exome sequencing identified a <i>TRAF7</i> p.Y563C missense mutation. The tumor was resected, and the patient is recovering well at 2 months with no evidence of local recurrence or distant disease. This report is the first known case of a <i>TRAF7</i>-mutated fibromyxoid spindle cell tumor of bone with the longest clinical follow-up reported to date.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432435","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":"Extrachromosomal DNA Detection and Ultrastructural Profiling in Lung and Colorectal Cancer Models","authors":"Astari Dwiranti,&nbsp;Gina Zulfa Nabila,&nbsp;Tiara Aulia Zalyanti,&nbsp;Shadira Anindieta Irdianto,&nbsp;Anom Bowolaksono","doi":"10.1002/gcc.70115","DOIUrl":"10.1002/gcc.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung and colorectal cancers are malignancies ranked as the leading cause of cancer-related mortality worldwide. Their high mortality rate is closely associated with drug resistance driven by cancer cell heterogeneity. One of the major contributors to this heterogeneity is the presence of extrachromosomal DNA (ecDNA), circular DNA fragments located outside linear chromosomes and generated through DNA damage. ecDNA is found exclusively in cancer cells, frequently carries highly amplified oncogenes, and contributes to cancer aggressiveness. To date, no study has characterized ecDNA in A549 and HT-29 cells, representative lung and colorectal cancer cell lines. This study aimed to detect and characterize ecDNA in A549 and HT-29 cells using Giemsa staining, DAPI staining, and scanning electron microscopy (SEM). Our findings revealed the presence of ecDNA, with the percentage of 15% in A549 and 10% of HT-29 cells from the total of 180 metaphase spread chromosomes. Among these, some spreads contained a single ecDNA and two ecDNA elements, either solitary or paired. The ecDNA area ranged from 0.537 μm² to 1.162 μm², with an average of 0.85 μm² in A549 cells. The fluorescence intensity of ecDNA ranged from 152.204 A.U. to 196.109 A.U., with an average of 179.847 A.U. While the ecDNA of HT-29 exhibited an average area of 0.455 μm² with an average DAPI fluorescence intensity of 102.747 A.U. SEM imaging further revealed ring-like circular structures with an area consistent with previously reported ecDNA ultrastructural characteristics. These results suggest that ecDNA is present across different cancer cell lines and may serve as a potential biomarker as well as a promising target for future cancer therapies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377129","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}