Genes, Chromosomes & Cancer最新文献

{"title":"Associations of Dietary Intake Traits and Aging Indicators With Colorectal Cancer: A Mendelian Randomization Study","authors":"Yuanlong Chi,&nbsp;Bao Lin,&nbsp;Shijie Sun,&nbsp;Hongjian Zhang,&nbsp;Changqing Lin,&nbsp;Zhen Zhang","doi":"10.1002/gcc.70149","DOIUrl":"10.1002/gcc.70149","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a major global health burden with an increasing incidence among younger adults. High-glycemic food intake and biological aging have been proposed as potential risk factors for CRC, but their causal relationships and underlying mechanisms remain unclear. We conducted a two-sample Mendelian randomization (MR) study using large-scale genome-wide association study summary data to evaluate the genetic associations of 25 high-glycemic food intake traits and five aging-related indicators, including GrimAge acceleration, intrinsic epigenetic age acceleration, PhenoAge acceleration, Hannum age acceleration, and mitochondrial DNA copy number, with CRC risk. Two-step MR was used to explore potential mediating role of aging indicators. MR analyses showed nominally significant positive associations of intake of sugar added to tea (OR = 1.307, 95% CI: 1.033–1.655, <i>p</i> = 0.026, FDR = 0.216) and doughnut intake (OR = 2.524, 95% CI: 1.317–4.835, <i>p</i> = 0.005, FDR = 0.131) with CRC risk, whereas yogurt intake was nominally associated with lower CRC risk (OR = 0.755, 95% CI: 0.596–0.958, <i>p</i> = 0.020, FDR = 0.216). These food–CRC associations did not survive FDR correction and should therefore be interpreted as suggestive evidence. GrimAge acceleration showed a positive genetic association with CRC risk (OR = 1.102, 95% CI: 1.039–1.169, <i>p</i> = 0.001). Mediation analysis suggested that GrimAge acceleration may partly mediate the association between intake of sugar added to tea and CRC risk, with an estimated mediated proportion of 36.1%. These findings provide genetic evidence suggesting potential links among specific high-glycemic food intake traits, epigenetic aging, and CRC risk; however, mediation finding did not pass strict significance testing and requires validation in larger and independent datasets.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264239","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":"Primary Tumor-Associated Loss of the Y Chromosome and Clinical Outcome in Metastatic Colorectal Cancer","authors":"Anaëlle Isnard,&nbsp;Marie Decraecker,&nbsp;Benjamin Fernandez,&nbsp;Denis Smith,&nbsp;Pierre Dubus,&nbsp;Sandrine Dabernat,&nbsp;Olivier Mansier,&nbsp;Samuel Amintas","doi":"10.1002/gcc.70147","DOIUrl":"10.1002/gcc.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alterations of the Y chromosome are frequent events in solid tumors, yet their biological and clinical significance remains incompletely understood. In colorectal cancer (CRC), recent studies have suggested context-dependent roles of Y-linked genes in tumor progression, while the impact of tumor-associated loss of the Y chromosome (LoY) in metastatic disease has not been clearly established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed primary tumor samples from 91 male patients with metastatic CRC treated at a single institution. Tumor LoY status was assessed using a droplet digital PCR–based assay. Associations between LoY, clinicopathological characteristics, <i>KRAS/BRAF</i> mutation status, and patient outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated. Exploratory analyses of TCGA-COAD/READ data were performed using chromosome Y copy-number segment data, mutation data, and survival information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tumor LoY was detected in 46 cases (50.5%) and was more frequent in rectal cancers (<i>p</i> = 0.038). LoY was not associated with age, microsatellite instability status, <i>KRAS</i> or <i>BRAF</i> mutations. While PFS did not differ according to LoY status, OS was longer in patients with LoY-positive tumors (<i>p</i> = 0.046). In multivariable analysis, LoY showed a non-significant trend toward improved OS (HR = 0.52, 95% CI: 0.25–1.10; <i>p</i> = 0.07). In exploratory TCGA analyses, chromosome Y copy-number signal did not significantly differ between colon and rectal cancers, but lower chromosome Y signal was associated with worse OS, particularly in TCGA-COAD after adjustment for age and <i>KRAS</i>/<i>BRAF</i> status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>LoY is a frequent chromosomal alteration in metastatic CRC and appears enriched in rectal primary tumors in our cohort. Its association with clinical outcome may depend on disease stage, molecular background, and analytical methodology. These findings support further investigation of Y chromosome loss as a context-dependent biomarker in CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251026","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":"Cytogenetic and Molecular Analysis of a “Double-Hit” RUNX1 Including a RUNX1 p.Trp279* and a Cryptic Novel t(6;21)(q25;q22)/RUNX1::ARID1B in Acute Myeloid Leukemia","authors":"Rolando García,&nbsp;Jing Xu,&nbsp;Lan Yu,&nbsp;Kalayarasan Srinivasan,&nbsp;Sharon Koorse Germans,&nbsp;Olga Weinberg,&nbsp;Franklin Fuda,&nbsp;Weina Chen,&nbsp;Prasad Koduru","doi":"10.1002/gcc.70148","DOIUrl":"10.1002/gcc.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Alterations involving <i>RUNX1</i> are recurrent in hematologic malignancies and contribute to disease pathogenesis via dysregulation of transcriptional factors essential for hematopoiesis. Here, we report an acquired alteration in both alleles of <i>RUNX1</i>; one is a truncating mutation and the second is a novel <i>RUNX1::ARID1B</i> identified in acute myeloid leukemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bone marrow samples were assessed by morphologic examination and flow cytometry. Cytogenetic analysis was performed using conventional G-banded karyotyping and fluorescence in situ hybridization (FISH). Molecular profiling was performed using next-generation sequencing (NGS) for single nucleotide changes, copy number variations, gene fusions, and expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Morphology showed large-sized myeloblasts that are CD34+ and CD45+ (dim) consistent with acute myeloid leukemia. Genetic analysis of diagnostic specimen showed normal karyotype and FISH results but detected mutations in <i>IDH1</i> and <i>RUNX1</i>. Cytogenetic analysis of a specimen at relapse showed complex abnormal karyotype and FISH detected <i>RUNX1</i> rearrangement with 6q25. NGS identified this rearrangement as <i>RUNX1::ARID1B</i>. Thus, at this stage leukemia cells had “double-hit” abnormality in <i>RUNX1</i>. Gene transcript evaluation showed elevated levels of transcripts of both <i>RUNX1</i> and <i>ARIDB1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study expands the spectrum of <i>RUNX1</i> fusions and highlights the integral diagnostic value of morphology, flow cytometry, cytogenetics, FISH, and NGS analyses for broad structural variant detection in clinical practice. Furthermore, the truncating mutation in one allele of <i>RUNX1</i> and <i>RUNX1</i>::<i>ARID1B</i> of the second allele detected with advanced disease suggests the possibility of combined transcriptional and chromatin regulatory alterations in disease recurrence in the patient.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148224222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Chapter for Genes, Chromosomes and Cancer","authors":"Martin Fischer","doi":"10.1002/gcc.70150","DOIUrl":"10.1002/gcc.70150","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148217378","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":"Detecting Rare ALK Gene Fusions in Unclassified Spindle Cell Lung Tumors Using Anchored Multiplex PCR/Targeted RNA Next-Generation Sequencing","authors":"Katsuhiro Masago,&nbsp;Katsutoshi Seto,&nbsp;Eiichi Sasaki,&nbsp;Yasuko Fujita,&nbsp;Shiro Fujita,&nbsp;Yoshitsugu Horio,&nbsp;Hirokazu Matsushita,&nbsp;Hiroaki Kuroda","doi":"10.1002/gcc.70146","DOIUrl":"https://doi.org/10.1002/gcc.70146","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary spindle cell tumors are aggressive neoplasms with limited systemic treatment options, although a subset may harbor actionable genomic alterations. Because conventional fusion assays may miss rearrangements involving atypical or previously uncharacterized partners, we systematically investigated oncogenic fusions in pulmonary spindle cell tumors using anchored multiplex PCR-based targeted RNA sequencing. Formalin-fixed, paraffin-embedded tumor samples from 11 surgically resected pulmonary spindle cell tumors, excluding metastatic sarcomas, were analyzed using the FusionPlex Sarcoma panel supplemented with custom primers for RET, NTRK1, NTRK2, and NRG1. Two tumors (18.2%) harbored <i>ALK</i> fusions, identified as <i>PPFIBP1</i>::<i>ALK</i> and <i>SYCL3</i>::<i>ALK</i>. Both tumors showed positive <i>ALK</i> immunohistochemical staining. Histologically, the <i>PPFIBP1::ALK-positive</i> tumor was composed of spindle-shaped cells with a layered architecture, whereas the <i>SYCL3::ALK-positive</i> tumor showed relatively round cells arranged in clusters with collagenous stroma, highlighting the morphologic heterogeneity of <i>ALK</i>-rearranged pulmonary spindle cell tumors. These findings expand the molecular spectrum of pulmonary spindle cell tumors and identify rare <i>ALK</i> fusion partners in this setting. Our results support the incorporation of <i>ALK</i> immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of <i>ALK</i>-directed therapy in these rare tumors.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148103203","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":"Detecting Rare ALK Gene Fusions in Unclassified Spindle Cell Lung Tumors Using Anchored Multiplex PCR/Targeted RNA Next-Generation Sequencing","authors":"Katsuhiro Masago,&nbsp;Katsutoshi Seto,&nbsp;Eiichi Sasaki,&nbsp;Yasuko Fujita,&nbsp;Shiro Fujita,&nbsp;Yoshitsugu Horio,&nbsp;Hirokazu Matsushita,&nbsp;Hiroaki Kuroda","doi":"10.1002/gcc.70146","DOIUrl":"https://doi.org/10.1002/gcc.70146","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary spindle cell tumors are aggressive neoplasms with limited systemic treatment options, although a subset may harbor actionable genomic alterations. Because conventional fusion assays may miss rearrangements involving atypical or previously uncharacterized partners, we systematically investigated oncogenic fusions in pulmonary spindle cell tumors using anchored multiplex PCR-based targeted RNA sequencing. Formalin-fixed, paraffin-embedded tumor samples from 11 surgically resected pulmonary spindle cell tumors, excluding metastatic sarcomas, were analyzed using the FusionPlex Sarcoma panel supplemented with custom primers for RET, NTRK1, NTRK2, and NRG1. Two tumors (18.2%) harbored <i>ALK</i> fusions, identified as <i>PPFIBP1</i>::<i>ALK</i> and <i>SYCL3</i>::<i>ALK</i>. Both tumors showed positive <i>ALK</i> immunohistochemical staining. Histologically, the <i>PPFIBP1::ALK-positive</i> tumor was composed of spindle-shaped cells with a layered architecture, whereas the <i>SYCL3::ALK-positive</i> tumor showed relatively round cells arranged in clusters with collagenous stroma, highlighting the morphologic heterogeneity of <i>ALK</i>-rearranged pulmonary spindle cell tumors. These findings expand the molecular spectrum of pulmonary spindle cell tumors and identify rare <i>ALK</i> fusion partners in this setting. Our results support the incorporation of <i>ALK</i> immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of <i>ALK</i>-directed therapy in these rare tumors.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148103213","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":"Rhabdomyosarcoma With Alveolar Morphology and a Novel NCOA1::ZNF143 Fusion in a 4-Year-Old Girl: A Case Report","authors":"Anastasia S. Sharlai,&nbsp;Tatyana S. Stradomskaya,&nbsp;Denis Y. Kachanov,&nbsp;Alexander E. Druy,&nbsp;Agnesa V. Panferova,&nbsp;Ruslan Abasov,&nbsp;Nikolai S. Grachev,&nbsp;Dmitry M. Konovalov","doi":"10.1002/gcc.70145","DOIUrl":"https://doi.org/10.1002/gcc.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Rhabdomyosarcoma with alveolar morphology is a diagnostically challenging tumor pattern, particularly in cases lacking canonical <i>FOXO1</i>-associated fusions. In the current WHO framework, molecular fusion status plays a central role in classification and risk stratification. However, a subset of tumors lacks canonical rearrangements and harbors alternative genetic events. We report a case of a 4-year-old girl with a massive parameningeal rhabdomyosarcoma presenting with cranial nerve dysfunction and airway compromise. Histological examination confirmed rhabdomyosarcoma with alveolar morphology. Fluorescence in situ hybridization revealed no rearrangements of <i>FOXO1</i> or <i>PAX3</i>. Targeted RNA sequencing identified a novel <i>NCOA1::ZNF143</i> fusion transcript. Despite intensive multimodal treatment including chemotherapy, radiotherapy, surgery, and metronomic therapy, the disease demonstrated multiple relapses with subsequent metastatic progression involving the spinal cord and central nervous system, ultimately leading to a fatal outcome.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148103210","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":"Rhabdomyosarcoma With Alveolar Morphology and a Novel NCOA1::ZNF143 Fusion in a 4-Year-Old Girl: A Case Report","authors":"Anastasia S. Sharlai,&nbsp;Tatyana S. Stradomskaya,&nbsp;Denis Y. Kachanov,&nbsp;Alexander E. Druy,&nbsp;Agnesa V. Panferova,&nbsp;Ruslan Abasov,&nbsp;Nikolai S. Grachev,&nbsp;Dmitry M. Konovalov","doi":"10.1002/gcc.70145","DOIUrl":"https://doi.org/10.1002/gcc.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Rhabdomyosarcoma with alveolar morphology is a diagnostically challenging tumor pattern, particularly in cases lacking canonical <i>FOXO1</i>-associated fusions. In the current WHO framework, molecular fusion status plays a central role in classification and risk stratification. However, a subset of tumors lacks canonical rearrangements and harbors alternative genetic events. We report a case of a 4-year-old girl with a massive parameningeal rhabdomyosarcoma presenting with cranial nerve dysfunction and airway compromise. Histological examination confirmed rhabdomyosarcoma with alveolar morphology. Fluorescence in situ hybridization revealed no rearrangements of <i>FOXO1</i> or <i>PAX3</i>. Targeted RNA sequencing identified a novel <i>NCOA1::ZNF143</i> fusion transcript. Despite intensive multimodal treatment including chemotherapy, radiotherapy, surgery, and metronomic therapy, the disease demonstrated multiple relapses with subsequent metastatic progression involving the spinal cord and central nervous system, ultimately leading to a fatal outcome.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 6","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148103209","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093102","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 5","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148091314","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}