Genes, Chromosomes & Cancer最新文献

{"title":"Genetic Heterogeneity in Cellular Angiofibromas","authors":"Ioannis Panagopoulos,&nbsp;Kristin Andersen,&nbsp;Ingvild Lobmaier,&nbsp;Marius Lund-Iversen","doi":"10.1002/gcc.23262","DOIUrl":"10.1002/gcc.23262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the <i>RB1</i> gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (<i>PLAG1</i>). In tumor 2, the cathepsin B (<i>CTSB</i>) fused to <i>PLAG1</i> (<i>CTSB::PLAG1</i>) while in tumor 3, the mir-99a-let-7c cluster host gene (<i>MIR99AHG</i>) fused to <i>PLAG1</i> (<i>MIR99AHG::PLAG1</i>), both leading to elevated expression of <i>PLAG1</i> and insulin growth factor 2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves <i>PLAG1</i>-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906400","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":"Hereditary Colorectal Cancer and Polyposis Syndromes Caused by Variants in Uncommon Genes","authors":"Ahmed Bouras,&nbsp;Aurélie Fabre,&nbsp;Hélène Zattara,&nbsp;Sandrine Handallou,&nbsp;Françoise Desseigne,&nbsp;Caroline Kientz,&nbsp;Fabienne Prieur,&nbsp;Magalie Peysselon,&nbsp;Clémentine Legrand,&nbsp;Laura Calavas,&nbsp;Jean-Christophe Saurin,&nbsp;Qing Wang","doi":"10.1002/gcc.23263","DOIUrl":"10.1002/gcc.23263","url":null,"abstract":"<p>A substantial number of hereditary colorectal cancer (CRC) and colonic polyposis cannot be explained by alteration in confirmed predisposition genes, such as mismatch repair (MMR) genes, <i>APC</i> and <i>MUTYH</i>. Recently, a certain number of potential predisposition genes have been suggested, involving each a small number of cases reported so far. Here, we describe the detection of rare variants in the <i>NTLH1</i>, <i>AXIN2</i>, <i>RNF43</i>, <i>BUB1</i>, and <i>TP53</i> genes in nine unrelated patients who were suspected for inherited CRC and/or colonic polyposis. Seven of them were classified as pathogenic or likely pathogenic variants (PV/LPV). Clinical manifestations of carriers were largely consistent with reported cases with, nevertheless, distinct characteristics. PV/LPV in these uncommon gene can be responsible for up to 2.7% of inherited CRC or colonic polyposis syndromes. Our findings provide supporting evidence for the role of these genes in cancer predisposition, and contribute to the determination of related cancer spectrum and cancer risk for carriers, allowing for the establishment of appropriate screening strategy and genetic counseling in affected families.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906401","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":"TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition","authors":"Vladimir Lazarevic,&nbsp;Henrik Lilljebjörn,&nbsp;Linda Olsson-Arvidsson,&nbsp;Christina Orsmark-Pietras,&nbsp;Helena Ågerstam","doi":"10.1002/gcc.23261","DOIUrl":"10.1002/gcc.23261","url":null,"abstract":"<p>Chromosomal rearrangements involving Janus kinase 2 (<i>JAK2</i>) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of <i>JAK2</i> fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (<i>TLE3)</i> and <i>JAK2</i> in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in <i>PTPN11</i> and <i>NRAS</i>. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with <i>PCM1::JAK2</i> and <i>BCR::JAK2</i> with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other <i>JAK2</i> fusion genes may benefit from treatment with JAK2 inhibitors.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893252","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":"Precision Diagnostics in Myeloid Malignancies: Development and Validation of a National Capture-Based Gene Panel","authors":"Christina Orsmark-Pietras,&nbsp;Anna Lyander,&nbsp;Claes Ladenvall,&nbsp;Björn Hallström,&nbsp;Anna Staffas,&nbsp;Hero Awier,&nbsp;Aleksandra Krstic,&nbsp;Panagiotis Baliakas,&nbsp;Gisela Barbany,&nbsp;Cecilia Brunhoff Håkansson,&nbsp;Anna Gellerbring,&nbsp;Anna Hagström,&nbsp;Eva Hellström-Lindberg,&nbsp;Gunnar Juliusson,&nbsp;Vladimir Lazarevic,&nbsp;Arielle Munters,&nbsp;Tatjana Pandzic,&nbsp;Mia Wadelius,&nbsp;Joel Ås,&nbsp;Linda Fogelstrand,&nbsp;Valtteri Wirta,&nbsp;Richard Rosenquist,&nbsp;Lucia Cavelier,&nbsp;Thoas Fioretos,&nbsp;the SciLifeLab Clinical Genomics Platform and Genomic Medicine Sweden","doi":"10.1002/gcc.23257","DOIUrl":"https://doi.org/10.1002/gcc.23257","url":null,"abstract":"<p>Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates. The GMS-MGP displayed uniform coverage across all targets, including recognized difficult GC-rich areas. The validation of 117 previously described somatic variants showed a 100% concordance with a limit-of-detection of a 0.5% variant allele frequency (VAF), achieved by utilizing error correction and filtering against a panel-of-normals. A national interlaboratory comparison investigating 56 somatic variants demonstrated highly concordant results in both detection rate and reported VAFs. In addition, prospective analysis of 323 patients analyzed with the GMS-MGP as part of standard-of-care identified clinically significant genes as well as recurrent mutations in less well-studied genes. In conclusion, the GMS-MGP workflow supports sensitive detection of all clinically relevant genes, facilitates novel findings, and is, based on the capture-based design, easy to update once new guidelines become available. The GMS-MGP provides an important step toward nationally harmonized precision diagnostics of myeloid malignancies.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730281","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":"Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance","authors":"Anna Djos,&nbsp;Johanna Svensson,&nbsp;Jennie Gaarder,&nbsp;Ganesh Umapathy,&nbsp;Staffan Nilsson,&nbsp;Torben Ek,&nbsp;Hartmut Vogt,&nbsp;Kleopatra Georgantzi,&nbsp;Ingrid Öra,&nbsp;Catarina Träger,&nbsp;Per Kogner,&nbsp;Tommy Martinsson,&nbsp;Susanne Fransson","doi":"10.1002/gcc.23260","DOIUrl":"https://doi.org/10.1002/gcc.23260","url":null,"abstract":"<p>Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an <i>MYCN</i>-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. <i>KDM5D</i>, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and <i>KDM5D</i> has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730282","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":"The Variable Genomic Landscape During Osteosarcoma Progression: Insights From a Longitudinal WGS Analysis","authors":"Debora M. Meijer,&nbsp;Dina Ruano,&nbsp;Inge H. Briaire-de Bruijn,&nbsp;Pauline M. Wijers-Koster,&nbsp;Michiel A. J. van de Sande,&nbsp;Hans Gelderblom,&nbsp;Anne-Marie Cleton-Jansen,&nbsp;Noel F. C. C. de Miranda,&nbsp;Marieke L. Kuijjer,&nbsp;Judith V. M. G. Bovée","doi":"10.1002/gcc.23253","DOIUrl":"10.1002/gcc.23253","url":null,"abstract":"<p>Osteosarcoma is a primary bone tumor that exhibits a complex genomic landscape characterized by gross chromosomal abnormalities. Osteosarcoma patients often develop metastatic disease, resulting in limited therapeutic options and poor survival rates. To gain knowledge on the mechanisms underlying osteosarcoma heterogeneity and metastatic process, it is important to obtain a detailed profile of the genomic alterations that accompany osteosarcoma progression. We performed WGS on multiple tissue samples from six patients with osteosarcoma, including the treatment naïve biopsy of the primary tumor, resection of the primary tumor after neoadjuvant chemotherapy, local recurrence, and distant metastases. A comprehensive analysis of single-nucleotide variants (SNVs), structural variants, copy number alterations (CNAs), and chromothripsis events revealed the genomic heterogeneity during osteosarcoma progression. SNVs and structural variants were found to accumulate over time, contributing to an increased complexity of the genome of osteosarcoma during disease progression. Phylogenetic trees based on SNVs and structural variants reveal distinct evolutionary patterns between patients, including linear, neutral, and branched patterns. The majority of osteosarcomas showed variable copy number profiles or gained whole-genome doubling in later occurrences. Large proportions of the genome were affected by loss of heterozygosity (LOH), although these regions remain stable during progression. Additionally, chromothripsis is not confined to a single early event, as multiple other chromothripsis events may appear in later occurrences. Together, we provide a detailed analysis of the complex genome of osteosarcomas and show that five of six osteosarcoma genomes are highly dynamic and variable during progression.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633091","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":"Fusion Genes Landscape of Lung Cancer Patients From Inner Mongolia, China","authors":"Lan Yu,&nbsp;Jinyang Liu,&nbsp;Jianchao Jia,&nbsp;Jie Yang,&nbsp;Ruiying Tong,&nbsp;Xiao Zhang,&nbsp;Yun Zhang,&nbsp;Songtao Yin,&nbsp;Junlin Li,&nbsp;Dejun Sun","doi":"10.1002/gcc.23258","DOIUrl":"10.1002/gcc.23258","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of <i>ALK</i> and <i>RET</i> fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: <i>SLC34A2-EPHB1</i>, <i>CCT6P3-GSTP1</i>, <i>BARHL2-APC</i>, <i>HRAS-MELK</i>, <i>FAM134B-ERBB2</i>, <i>ABCB1-GIPC1</i>, <i>GPR98-ALK</i>, and <i>FAM134B-SALL1</i>. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with <i>SLC34A2-EPHB1</i>, <i>CCT6P3-GSTP1</i>, and <i>BARHL2-APC</i> fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with <i>HRAS-MELK</i>, <i>FAM134B-ERBB2</i>, and <i>ABCB1-GIPC1</i> fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619769","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":"Nanopore DNA Sequencing Detected Chromothripsis-Induced PAFAH1B1::USP6 Rearrangement in Periosteal Solid Aneurysmal Bone Cyst Initially Diagnosed as Osteosarcoma","authors":"Naohiro Makise,&nbsp;Jason Lin,&nbsp;Hajime Kageyama,&nbsp;Hideyuki Kinoshita,&nbsp;Hiroto Kamoda,&nbsp;Yoko Hagiwara,&nbsp;Mariko Oikawa,&nbsp;Takahiro Sugiyama,&nbsp;Hidetada Kawana,&nbsp;Akinobu Araki,&nbsp;Tsukasa Yonemoto,&nbsp;Masahito Kawazu,&nbsp;Makiko Itami","doi":"10.1002/gcc.23254","DOIUrl":"10.1002/gcc.23254","url":null,"abstract":"<div>\u0000 \u0000 <p>An aneurysmal bone cyst (ABC) is a benign bone neoplasm that typically occurs during the first and second decades of life. ABC usually presents as a rapidly growing intramedullary expansile mass with multiple blood-filled cysts in the metaphysis of the long tubular bones. Here, we report a case of a periosteal solid ABC that was initially diagnosed as a high-grade surface osteosarcoma. A 10-year-old male was referred to our hospital for swelling and tenderness of the left upper arm. Radiography revealed periosteal mass without fluid–fluid levels. On performing open biopsy, the tumor showed hypercellular proliferation of uniform spindle to epithelioid cells with brisk mitotic activity (up to 12/2 mm²) and lace-like osteoid formation, which was diagnosed as a high-grade surface osteosarcoma. After one course of chemotherapy using adriamycin and cisplatin, peripheral sclerosis was conspicuous, which led to pathological review and revision of diagnosis as “possibly osteoblastoma.” The patient was disease-free for 4 years after marginal resection and curettage. Retrospective nanopore DNA sequencing unexpectedly detected a <i>PAFAH1B1::USP6</i> rearrangement. The fusion gene was further validated using reverse transcription-polymerase chain reaction and the diagnosis was revised to ABC. Chromothripsis involving chromosome 17 has also been identified. Methylation analysis classified the present tumor as an ABC or non-ossifying fibroma using t-distributed stochastic neighbor embedding and unsupervised hierarchical clustering. This case report highlights the utility of nanopore DNA sequencing for soft tissue and bone tumor diagnosis.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558641","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 Novel JAK2 Fusion in T-Cell Prolymphocytic Leukemia","authors":"Ozgur Can Eren,&nbsp;Robert Stuver,&nbsp;Ting Zhou,&nbsp;Michael Zaidinski,&nbsp;Alison J. Moskowitz,&nbsp;Steven M. Horwitz,&nbsp;Mark D. Ewalt,&nbsp;Yanming Zhang,&nbsp;Megan S. Lim","doi":"10.1002/gcc.23252","DOIUrl":"https://doi.org/10.1002/gcc.23252","url":null,"abstract":"<div>\u0000 \u0000 <p>T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell malignancy characterized by marked lymphocytosis, B symptoms, lymphadenopathy, and hepatosplenomegaly. There is no standard treatment approach, and in the absence of an allogeneic transplant, the prognosis remains poor. The disease-defining cytogenetic abnormality in T-PLL is the juxtaposition of the <i>TCL1-</i>family oncogene to the <i>TCR</i> gene enhancer locus primarily due to an inversion of chromosome 14, that is, inv(14). The application of next-generation sequencing technologies led to the discovery of highly recurrent gain-of-function mutations in <i>JAK1/3</i> and <i>STAT5B</i> in over 70% of T-PLL providing opportunities for therapeutic intervention using small molecule inhibitors. Additional genetic mechanisms that may contribute to the pathogenesis of T-PLL remain unknown. Herein we describe the identification of a novel gene fusion <i>SMCHD1::JAK2</i> resulting from a translocation between chromosome 9 and 18 involving <i>SMCHD1</i> exon 45 and <i>JAK2</i> exon 14 (t(9;18)(p24.1;p11.32)(chr9:g.5080171::chr18:g.2793269)), a previously undescribed genetic event in a patient with T-PLL harboring the key disease defining inv(14) resulting in rearrangement of <i>TCL1</i> and <i>TRA/D</i>. In this manuscript, we describe the clinical and genetic features of the patient's disease course over a 25-month post-treatment duration using ruxolitinib and duvelisib.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441387","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":"Identification of Rare EIF3E::RSPO2 Fusion in Recurrent and Aggressive Urachal Adenocarcinoma","authors":"Prerana Jha,&nbsp;Ruma Pengal,&nbsp;Minit Shah,&nbsp;Pooja Mahesh Kulkarni,&nbsp;Rohit Mishra,&nbsp;Nandini Menon,&nbsp;Narendranath Vikkath,&nbsp;Santosh Menon,&nbsp;Venkataramanan Ramachandran,&nbsp;Gagan Prakash,&nbsp;Vanita Noronha,&nbsp;Kumar Prabhash,&nbsp;Prashant Kumar","doi":"10.1002/gcc.23250","DOIUrl":"10.1002/gcc.23250","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Urachal cancer (UC) is a rare genitourinary malignancy arising from the urachus, an embryonic remnant of the placental allantois. Its diagnosis remains ambiguous with late-stage cancer detection and represents a highly aggressive disease. Due to its rarity, there is no clear consensus on molecular signatures and appropriate clinical management of UC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>We report a 45-year-old man with recurrent urachal adenocarcinoma (UA) treated with cystectomies, chemotherapy, and radiotherapy. The patient initially presented with hematuria and abdominal pain. Imaging revealed a nodular mass arising from the superior wall of the urinary bladder and extending to the urachus. Biopsy results suggested moderately differentiated UA with muscle layer involvement. The tumor recurred after 20 months, following which, another partial cystectomy was performed. Repeat progression was noted indicating highly aggressive disease. Targeted next-generation sequencing revealed the presence of <i>EIF3E</i>::<i>RSPO2</i> fusion, along with <i>BRAF</i> and <i>TP53</i> mutations, and <i>EGFR</i> gene amplification. This is the first case reporting the presence of this fusion in UA. Palliative medication and radiotherapy were administered to manage the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Current treatment modality of surgery may be effective in the early stages of recurrent UA; however, a standard chemotherapy and radiotherapy regimen is yet to be determined for advanced stages. The detection of the rare <i>EIF3E</i>::<i>RSPO2</i> fusion warrants further studies on the significance of this variant as a possible therapeutic target for improved clinical management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330671","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}