Genes, Chromosomes & Cancer最新文献

{"title":"Banding Karyotyping From Peripheral Blood Is a Useful Method for the Diagnostic Workup of Myelodysplastic Neoplasia and CMML","authors":"Cornelia Heusler,&nbsp;Barbara Hildebrandt,&nbsp;Felicitas Schulz,&nbsp;Kathrin Nachtkamp,&nbsp;Corinna Strupp,&nbsp;Valerie Flatten,&nbsp;Sascha Dietrich,&nbsp;Norbert Gattermann,&nbsp;Ulrich Germing","doi":"10.1002/gcc.70177","DOIUrl":"10.1002/gcc.70177","url":null,"abstract":"<p>This retrospective study involving 155 patients from the Düsseldorf MDS Registry compared cytogenetic banding from peripheral blood (PB) and bone marrow (BM) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). For 63 of these patients, paired PB and BM cytogenetic analyses were available that were conducted no more than 3 months apart. Concordant ISCN results were found in 81%, with no significant differences in the total number of metaphases or aberrant metaphases between PB and BM. Furthermore, IPSS-R/-M scorings, derived from PB and BM, turned out to be comparable, with only 7 out of 63 patients classified into a different cytogenetic risk category. This implies that aberrant clones are not underrepresented in PB and that cytogenetic findings from PB can reliably reflect those obtained from BM.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136296","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":"Round-to-Epithelioid Mesenchymal Tumor Harboring an MN1::BEND2 Fusion: Expanding the Morphologic Spectrum","authors":"Qiong-Yi Wang,&nbsp;Ko-Chin Chen,&nbsp;Wan-Shan Li,&nbsp;Fu-Chen Kuo,&nbsp;Hsuan-Ying Huang","doi":"10.1002/gcc.70180","DOIUrl":"10.1002/gcc.70180","url":null,"abstract":"<div>\u0000 \u0000 <p><i>MN1::BEND2</i> fusion is well established in CNS tumors but exceptionally rare in extracranial mesenchymal neoplasms. We report a subcutaneous upper-back tumor in a 41-year-old woman, composed of bland round-to-epithelioid cells with branching capillary vasculature and focal infiltrative growth. The tumor recurred 42 months after excision. Targeted RNA sequencing identified an in-frame <i>MN1</i> exon 1::<i>BEND2</i> exon 9 fusion, supported by Sanger sequencing and <i>MN1</i> break-apart FISH; Nuclear BEND2 immunoreactivity was an ancillary finding. Unlike two previously reported extracranial <i>MN1::BEND2</i>-harboring tumors with high-grade spindle-cell morphology and myofibroblastic differentiation, this tumor lacked overt high-grade nuclear features and myoid differentiation. This case broadens the morphologic spectrum of <i>MN1::BEND2</i> mesenchymal neoplasms. Limited reported cases, no meaningful follow-up after re-excision, and unsuccessful methylation profiling preclude conclusions regarding biologic behavior. BEND2 immunohistochemistry may serve an ancillary screen marker, but its sensitivity and specificity remain to be established, and molecular confirmation is required.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136299","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":"Dual INI1–BRG1-Deficient Pericardial Tumor With Rhabdoid Morphology and Clinical Benefit From DNA-Damaging Therapy","authors":"Jakub Czerwiński,&nbsp;Karolina Miarka-Walczyk,&nbsp;Zuzanna Urbańska,&nbsp;Aleksandra Hincz,&nbsp;Anna Marcinkiewicz,&nbsp;Tomasz Labuk,&nbsp;Rafał Czyżykowski,&nbsp;Agata Pastorczak,&nbsp;Marcin Braun","doi":"10.1002/gcc.70179","DOIUrl":"10.1002/gcc.70179","url":null,"abstract":"<div>\u0000 \u0000 <p>Primary pericardial <i>SMARCB1</i>-deficient tumors with rhabdoid morphology are exceptionally rare. We present an adult case of a primary <i>SMARCB1</i>-deficient pericardial tumor showing concurrent loss of INI1 (<i>SMARCB1</i>) and BRG1 (<i>SMARCA4</i>) expression, representing the third documented tumor with co-loss of these SWI/SNF subunits across tumor sites. Targeted RNA sequencing detected no pathogenic sequence variants or fusion transcripts and showed reduced <i>SMARCB1</i> and <i>SMARCA4</i> transcript abundance. DNA-based whole-exome sequencing (WES) identified no pathogenic or likely pathogenic sequence variants in either gene. High-resolution SNP microarray demonstrated a homozygous <i>SMARCB1</i> deletion with intact <i>SMARCA4</i>, establishing biallelic <i>SMARCB1</i> inactivation; BRG1 loss was accompanied by marked SMARCA4 transcript downregulation in the absence of a detectable SMARCA4 genomic alteration. In the clinicopathological context, the overall findings supported classification as a <i>SMARCB1</i>-deficient pericardial tumor with rhabdoid morphology. Following resection, postoperative imaging suggested residual or recurrent disease. Combined doxorubicin–ifosfamide chemotherapy and radical radiotherapy achieved a complete radiologic response. However, imaging 18 months after resection suggested multifocal pericardial recurrence, with disease control regained following similar treatment. This course is hypothesis-generating and may suggest sensitivity to DNA-damaging therapy in the setting of dual SWI/SNF deficiency.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136340","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":"Retrospective RNA Sequencing Reclassifies a Historical t(5;12) Eosinophilic Neoplasm From Presumed PDGFRB Rearrangement to ETV6::ACSL6","authors":"Frédéric Lambert,&nbsp;Rafael Fernandez Carazo,&nbsp;Benjamin Koopmansch,&nbsp;Elisa Dardenne,&nbsp;Pierre Sidon,&nbsp;Gaëlle Vertenoeil,&nbsp;Pierre Heimann","doi":"10.1002/gcc.70178","DOIUrl":"https://doi.org/10.1002/gcc.70178","url":null,"abstract":"<div>\u0000 \u0000 <p>The molecular interpretation of eosinophilic neoplasms harboring <i>t</i>(5;12) may be challenging because cytogenetic breakpoint assignments can suggest a <i>PDGFRB</i> rearrangement without identifying the underlying fusion. We retrospectively investigated a woman with a chronic eosinophilic myeloid neoplasm initially investigated in 2002, in whom a subsequent <i>t</i>(5;12)(q31 ~ q33;p13) raised suspicion of <i>PDGFRB</i> involvement. Contemporary molecular investigations failed to identify the rearrangement, and an empiric trial of imatinib produced no meaningful hematologic response. Seventeen years later, blast transformation was accompanied by persistence of <i>t</i>(5;12) and acquisition of del(9)(q22). Fluorescence in situ hybridization demonstrated <i>ETV6</i> rearrangement but no <i>PDGFRB</i> break-apart pattern, indicating <i>en bloc</i> translocation of the <i>PDGFRB</i> locus. Targeted RNA sequencing of archived RNA extracted from cryopreserved peripheral blood cells collected in 2004 subsequently identified a strong-evidence <i>ETV6::ACSL6</i> fusion joining exon 2 of <i>ETV6</i> to exon 2 of <i>ACSL6</i>, supported by 1847 reads and 218 unique start sites. Targeted myeloid DNA sequencing detected no mutation within the regions analyzed. Identification of <i>ETV6::ACSL6</i> shifted the biological interpretation away from presumed constitutive tyrosine kinase activation toward a proposed cytokine regulatory rewiring involving the 5q31 cytokine locus, consistent with published experimental evidence and the absence of response to imatinib. This case illustrates how contemporary RNA-based fusion detection can resolve a historically uncharacterized structural rearrangement and refine biological interpretation and therapeutic expectations, while documenting an unusually prolonged natural history of an <i>ETV6::ACSL6</i>-associated eosinophilic myeloid neoplasm.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100329","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":"Tumor Profile, Clinical Features, and Outcomes in Individuals With Constitutional Trisomy 8: A Systematic Review of Case Reports and Case Series","authors":"Ehsan Taherifard,&nbsp;Alexandre Theron,&nbsp;Erfan Taherifard,&nbsp;Motoi Nishi,&nbsp;Michel Vekemans,&nbsp;Daniel Satgé","doi":"10.1002/gcc.70176","DOIUrl":"https://doi.org/10.1002/gcc.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal disorder with poorly characterized cancer risk. This systematic review aimed at summarizing reported cases of malignancy and associated clinical outcomes in individuals with CT8M.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was conducted in PubMed, Scopus, Web of Science, Ichushi, and Google Scholar up to January 30, 2026, without restrictions on language and publication date. Case reports and case series reporting individuals with confirmed CT8M and malignancies were included. JBI Critical Appraisal Checklists were used to evaluate the quality of included studies. Data synthesis involved a descriptive approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-seven studies describing 47 individuals with CT8M and tumors were identified. A female predominance was observed (25/45, 55.5%), and age at malignancy diagnosis ranged from 1 to 84 years, with most cases occurring in childhood or adolescence. Over half of the individuals had a normal appearance (52.3%), while approximately one third exhibited a typical CT8M phenotype (28.5%). Hematologic malignancies predominated (82.9%), particularly, myelodysplastic syndromes (MDS) and acute myeloid leukemia. Importantly, 27.2% of individuals with MDS showed isolated trisomy 8 in bone marrow without additional cytogenetic abnormalities. Solid tumors were less frequent and were predominantly embryonal. Clinical outcomes were generally poor, and phenotypic severity or tissue-specific mosaic percentages did not appear to correlate with outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest a distinctive cancer profile characterized by a marked predominance of myeloid neoplasms, often with an onset several decades earlier than expected and in the absence of overt syndromic features. The observed pattern may reflect the biological consequences of increased gene dosage and transcriptional dysregulation associated with constitutional trisomy 8, although the underlying mechanisms remain uncertain. Targeted evaluation for CT8M may be particularly relevant in (i) pediatric patients with MDS, (ii) individuals with persistent trisomy 8 in bone marrow or peripheral blood with planned therapeutic interventions, and (iii) patients with subtle dysmorphic features rather than through universal screening approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 10","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099819","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 Reproducible Transcriptomic Program of Neurofibroma-to-Malignant Peripheral Nerve Sheath Tumor Transformation","authors":"Quanyu Jin,&nbsp;Zhenxuan Gao,&nbsp;Ze Zhang,&nbsp;Chenchen Kong,&nbsp;Jiaxin Liu,&nbsp;Aerman Abudurezhake,&nbsp;Lei Kou,&nbsp;Shuguang Cai,&nbsp;Wenqiang Yang,&nbsp;Qi Wang,&nbsp;Zhitao Li,&nbsp;Li Zhang","doi":"10.1002/gcc.70175","DOIUrl":"10.1002/gcc.70175","url":null,"abstract":"<div>\u0000 \u0000 <p>Malignant peripheral nerve sheath tumor (MPNST) carries the highest excess mortality of the cancers associated with neurofibromatosis Type 1, and usually arises from a neurofibroma. We asked whether the transcriptomic differences that distinguish MPNST from neurofibroma reproduce across independent cohorts, and whether a compact score derived from them transports between platforms. We meta-analyzed five public discovery cohorts of primary nerve-sheath tissue (113 MPNST, 79 neurofibromas; 3 platforms) and held out a sixth, independently generated cohort. Neurofibroma and MPNST tissue differed at 1489 genes in two opposing themes: up-regulated mitotic machinery (<i>TOP2A</i>, <i>EZH2</i>, <i>AURKA</i>) and loss of Schwann-cell identity (the transcription factors <i>SOX10</i> and <i>EGR2</i>, and the myelin genes <i>PMP2</i> and <i>MPZ</i>). These differences were reproducible. Among the significant genes assayed in all five cohorts, almost all changed in the same direction in everyone, and 93.3% of those detectable in the held-out cohort agreed in direction. Leave-one-cohort-out re-derivation of the pipeline gave a mean AUC of 0.90 across five folds (per-fold 0.84 to 0.97). <i>CD276</i> (B7-H3) was selectively up-regulated, whereas <i>CD274</i> and <i>PDCD1LG2</i> were not. The myelin marker <i>PMP2</i>, a readout chosen retrospectively after the held-out results were known, separated MPNST from neurofibroma in that cohort but left atypical and conventional neurofibromas unseparated (AUC 0.67, <i>p</i> = 0.10). A program score derived without the discovery cohort carrying survival data was associated with shorter survival there, an exploratory single-cohort association. The composition of a compact score varied with platform and preprocessing, so no fixed single-sample classifier is warranted.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012199","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":"Integrated Genomic Profiling of PTEN and TP53 in Cervical Neuroendocrine Carcinoma: Synergistic Roles With HER2/KRAS/PIK3CA and Implications for Precision Oncology","authors":"Huang-Pin Shen,&nbsp;Ming-Yung Lee,&nbsp;Yi-Ju Lee,&nbsp;An-Chi Chen,&nbsp;Chi-Kuan Chen,&nbsp;Wan-Ru Chao,&nbsp;Chih-Ping Han","doi":"10.1002/gcc.70173","DOIUrl":"10.1002/gcc.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuroendocrine carcinoma (NEC) of the uterine cervix is a rare, highly aggressive malignancy with a poor prognosis. Expanding upon our previous work, which identified frequent mutations in <i>HER2</i>, <i>KRAS</i>, and <i>PIK3CA</i> in this disease, we sought to refine the genomic landscape by characterizing alterations in <i>TP53</i> and <i>PTEN</i>, and their relationships with these oncogenic drivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genomic DNA from 12 cervical NECs with ≥ 50% tumor cellularity underwent targeted next-generation sequencing (NGS) using the Qiagen GeneRead DNAseq Targeted Panels V2. Variants were filtered against COSMIC and ClinVar, and the pathogenicity of missense changes was assessed with PolyPhen-2, with scores &gt; 0.85 considered probably damaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>PTEN</i> alterations were identified in 25.0% (3/12) of tumors, encompassing four truncating mutations (p.W111*, p.Q171*, p.Q245*, p.R335*) and three missense variants (p.R130Q, p.E394G, p.D395V). A <i>TP53</i> DNA-binding domain hotspot mutation, p.R273H, was detected in 8.33% (1/12). These tumor-suppressor lesions frequently co-occurred with oncogenic driver mutations, including <i>HER2/PTEN</i> (8.33%), <i>PIK3CA/PTEN</i> (8.33%), and a <i>KRAS/PTEN/TP53</i> “triple-hit” (8.33%), underscoring multipathway genomic complexity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest a genomic landscape consistent with a multihit hypothesis in cervical NEC, in which disruption of the reciprocal tumor-suppressive PTEN-p53 axis (25.0% and 8.33%, respectively) co-occurs with oncogenic <i>HER2</i>, <i>KRAS</i>, or <i>PIK3CA</i> alterations. Structural mapping indicates that <i>TP53</i> p.R273H gain-of-function mutations and <i>PTEN</i> loss-of-function variants are associated with sustained PI3K/AKT/mTOR pathway activation. Integrating <i>TP53</i> and <i>PTEN</i> status with oncogenic driver profiling may facilitate the identification of biologically defined subsets and inform precision therapeutic strategies for cervical NEC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012243","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":"Nano-RAPID: Integrated Diagnosis for Sarcoma Using a Nanopore Sequencer","authors":"Naohiro Makise,&nbsp;Jason Lin,&nbsp;Yuki Nakamura,&nbsp;Hajime Kageyama,&nbsp;Ryuta Kojima,&nbsp;Hideyuki Kinoshita,&nbsp;Hiroto Kamoda,&nbsp;Yoko Hagiwara,&nbsp;Mariko Oikawa,&nbsp;Takahiro Sugiyama,&nbsp;Akinobu Araki,&nbsp;Tsukasa Yonemoto,&nbsp;Masahito Kawazu,&nbsp;Makiko Itami","doi":"10.1002/gcc.70174","DOIUrl":"10.1002/gcc.70174","url":null,"abstract":"<div>\u0000 \u0000 <p>Pathological diagnosis of sarcoma is challenging. Although high-throughput sequencing and methylation array aid sarcoma diagnosis and are routine in high-income countries, access to these genetic/epigenetic analyses in many countries, including Japan, remains limited. Nanopore sequencing is an easy, fast, and cost-effective high-throughput sequencing alternative. Nanopore sequencers read long-read DNA to detect fusion DNA and 5-methyl-cytosine in single nucleotide resolution, enabling real-time basecalling for selective enrichment of regions of interest via “adaptive sampling.” Nanopore sequencing of Raw DNA with Adaptive sampling for Prompt Integrated Diagnosis (Nano-RAPID) was developed to test its diagnostic utility. This study included 22 retrospective and nine prospective cases. DNA extracted from fresh/frozen tissue was sequenced for 46–98 h, followed by approximately 12 h of data analysis. Consequently, disease-specific/characteristic fusion genes were detected in 10 retrospective and six prospective cases. Disease-specific single nucleotide variants were detected in three cases, while disease-specific amplifications were detected in two retrospective cases. Monosomy, trisomy, and chromosomal instability were also detected. Methylation analyses accurately classified 15 retrospective and five prospective cases. Collectively, correct tumor types were identified using at least one modality in 19 retrospective and nine prospective cases. Halving the consumables and re-analyzing 24-h data yielded nearly equivalent results, suggesting faster and cost-effective analyses. In conclusion, Nano-RAPID may be a promising adjunctive for sarcoma diagnosis. Nano-RAPID could be introduced in low-equipped hospitals to assist non-specialized pathologists diagnosing sarcoma. Since this study remains exploratory, further studies with larger cohort should be needed.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989737","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":"HPV-Associated Adenosquamous Carcinoma of the Oropharynx With a PARD3B::ERBB4 Fusion","authors":"Seddig Momenkhan,&nbsp;Jacques Blanc,&nbsp;Pierre Philouze,&nbsp;Jonathan Lopez,&nbsp;Francoise Descotes,&nbsp;Eudeline Alix,&nbsp;Camille Leonce,&nbsp;Ziyad Alsugair,&nbsp;Nazim Benzerdjeb","doi":"10.1002/gcc.70165","DOIUrl":"https://doi.org/10.1002/gcc.70165","url":null,"abstract":"<p>Head and neck carcinomas can be diagnostically challenging because of their diverse histologic subtypes. We report a case of a 55-year-old male presenting with right-sided cervical adenopathy, in whom imaging revealed a cystic lesion that was subsequently confirmed to be metastatic from a lesion at the base of the tongue. Histological examination of the lesion at the base of the tongue demonstrated a biphasic tumor proliferation composed of nonkeratinized basaloid cells arranged in cohesive lobules, with focal small ductal structures. Immunohistochemistry highlighted the biphasic morphology, with strong nuclear expression of p40/p63 in the abluminal cells and prominent membranous staining of CEA and CK7 in the luminal cells. Ancillary testing further characterized the lesion, identifying an HPV16 by DNA PCR. RNA sequencing revealed a <i>PARD3B::ERBB4</i> fusion involving <i>PARD3B</i> exon 13 and <i>ERBB4</i> exon 17, while targeted next-generation sequencing identified a <i>KRAS</i> exon 2 c.35G&gt;A (p.Gly12Asp) mutation. Microdissection-based analysis confirmed the same <i>KRAS</i> mutation in both the glandular and squamous components, supporting a shared clonal origin. This case highlights the clinicopathologic complexity of HPV-associated adenosquamous carcinoma and expands the molecular spectrum of head and neck tumors through identification of a <i>PARD3B</i>::<i>ERBB4</i> fusion.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943293","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":"IRF8 Suppresses Hepatocellular Carcinoma Progression Through LIAS-Dependent IFN Production and Cuproptosis Activation","authors":"Li Zhu,&nbsp;Zhaoxia Hu,&nbsp;Bei Wu,&nbsp;Meng Duan,&nbsp;Li Wang,&nbsp;Ruiqing Hu,&nbsp;Hongfan Liao,&nbsp;Xiaosi Zhao,&nbsp;Yilan Zeng,&nbsp;Lei Li,&nbsp;Yuelian Wang,&nbsp;Mei Luo","doi":"10.1002/gcc.70172","DOIUrl":"10.1002/gcc.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Cuproptosis is a novel form of regulated cell death closely linked to tumor progression. Although interferon regulatory factors (IRFs) exert tumor-suppressive effects in various cancers, its precise regulatory mechanisms concerning cuproptosis in HCC remain largely elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IRF8 expression was evaluated in clinical HCC specimens and cell lines. Gain- and loss-of-function assays were conducted. Underlying transcriptional mechanisms were elucidated using ChIP-qPCR and dual-luciferase reporter assays. Subcutaneous nude mouse xenograft models were utilized to validate in vivo phenotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IRF8 was significantly downregulated in HCC. IRF8 overexpression induced oxidative stress and cuproptosis, as evidenced by excessive intracellular copper accumulation, elevated reactive oxygen species (ROS), and lipid peroxidation. Mechanistically, IRF8 directly bound to the promoter region of lipoyl synthase (LIAS) to activate its transcription. Phenotypic rescue assays confirmed that LIAS is indispensable for IRF8-induced interferon (IFN-α/β) production, copper engorgement, and cuproptosis. Furthermore, in vivo xenograft models demonstrated that IRF8 profoundly impeded tumor growth, an effect that was effectively abrogated by LIAS silencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IRF8 inhibits HCC progression by directly upregulating LIAS to instigate lethal cuproptosis and interferon responses. The IRF8/LIAS axis may serve as a potential mechanistic basis and candidate axis for developing HCC therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"65 9","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919587","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}