Genes, Chromosomes & Cancer最新文献

{"title":"Pediatric Mesenchymal Tumor With MN1::TAF3 Fusion","authors":"Chikako Sato,&nbsp;Masanaka Sugiyama,&nbsp;Taisuke Mori,&nbsp;Shogo Nishino,&nbsp;Kayoko Tao,&nbsp;Chitose Ogawa,&nbsp;Akihiko Yoshida","doi":"10.1002/gcc.70009","DOIUrl":"10.1002/gcc.70009","url":null,"abstract":"<div>\u0000 \u0000 <p><i>MN1</i> fusion is emerging as oncogenic in soft-tissue tumors. Here, we provided detailed clinicopathological documentation of a tumor with <i>MN1</i>::<i>TAF3</i> fusion. The tumor developed on the face of an 8-year-old boy and did not recur or metastasize for 5 years after surgery without adjuvant therapy. Histologically, the tumor predominantly comprised sheets and nests of atypical, mildly pleomorphic epithelioid cells. Mallory body-like eosinophilic cytoplasmic inclusions, small round cells, and fascicles of spindle cells were focally observed. Mitotic activity was high, and focal necrosis was present. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3 in the epithelioid cell component but otherwise showed nonspecific phenotypes. Targeted RNA sequencing identified an in-frame <i>MN1</i> (exon 1)::<i>TAF3</i> (exon 3) fusion transcript. We validated the transcript with reverse transcription-polymerase chain reaction, Sanger sequencing, and <i>MN1</i> break-apart fluorescence in situ hybridization. <i>MN1</i>::<i>TAF3</i> was previously listed without details in a large-scale sequencing study involving a pediatric round cell sarcoma in the orbit, raising the possibility that these tumors might form a coherent group.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638640","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":"Differential Expression of Proteins and Genes at the Tumor-Brain Interface in Invasive Meningioma","authors":"Kornwika Senglek,&nbsp;Chinachote Teerapakpinyo,&nbsp;Nutchawan Jittapiromsak,&nbsp;Pakrit Jittapiromsak,&nbsp;Irin Lertparinyaphorn,&nbsp;Paul Scott Thorner,&nbsp;Shanop Shuangshoti","doi":"10.1002/gcc.70007","DOIUrl":"10.1002/gcc.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Most meningiomas are dural-based extra-axial tumors in close contact with the brain. Expression of genes and proteins at the tumor-brain interface in brain-invasive meningioma is basically unknown. Using the NanoString pan-cancer panel, differential expression of genes in the invasive edge versus main tumor body was determined in 12 invasive meningiomas (comprising the discovery cohort), and 6 candidate genes: <i>DTX1</i>, <i>RASGRF1</i>, <i>GRIN1</i>, <i>TNR</i>, <i>IL6</i>, and <i>NR4A1</i>, were identified. By immunohistochemistry, DTX1 and RASGRF1 expression correlated with gene expression, and were studied in an expanded cohort of 21 invasive and 15 noninvasive meningiomas, together with Ki-67. Significantly higher expression of DTX1, RASGFR1, and Ki-67 was found in the invasive edge compared with the main tumor body. Increased expression of RASGRF1 and Ki-67 was more clearly associated with brain invasion. The situation with DTX1 was less definitive since increased expression was observed in meningiomas both at the invasive edge and when in close contact with brain but without invasion. Pathway analyses identified significant links between <i>DTX1</i> and <i>RASGRF1</i> and key biological processes, including cell–cell adhesion, and signaling pathways including Notch, RAS, MAPK, and Rho. Higher expression of DTX1, RASGRF1, and Ki-67 in the brain-invasive area of meningiomas suggests that these proteins play a role in the process of brain invasion.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLI1, CDK4, and MDM2 Co-Amplification Gastric Plexiform Fibromyxoma: A Case Report and Literature Review","authors":"Shihui Zhang,&nbsp;Ye Yang,&nbsp;Jianwei Li,&nbsp;Zheng Li,&nbsp;Weihua Li,&nbsp;Susheng Shi","doi":"10.1002/gcc.70005","DOIUrl":"10.1002/gcc.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>Plexiform fibromyxoma (PF) is a rare mesenchymal tumor that primarily occurs in gastric origin with a benign behavior. PF commonly harbors the <i>MALAT1::GLI1</i> fusion gene. Here, we describe a case of a 36-year-old female with a PF. Abdominal computed tomography (CT) showed a 3.3 cm mass in the stomach. She underwent laparoscopic partial gastrectomy. Immunohistochemistry (IHC) of the tumor revealed strongly positive staining for <i>CD34</i>, <i>SDHB</i>, <i>STAT6</i>, <i>MDM2</i>, and <i>CDK4</i>. And the tumor showed <i>TP53</i> mutant expression. Next-generation sequencing (NGS) comprehensive genomic profiling identified <i>GLI1</i>, <i>CDK4</i>, and <i>MDM2</i> co-amplification and <i>TP53</i> mutations. Here, we first report a case of a young woman with a PF harboring co-amplification of <i>GLI1</i>, <i>CDK4</i>, and <i>MDM2</i> genes. The patient underwent complete removal of the tumor without the use of radiotherapy or chemotherapy. No recurrence was observed during the follow-up period of 8 months. This study aims to improve our understanding of PF by analyzing the clinicopathological characteristics of this case, including immunohistochemical (IHC) and genetic examination, and reviewing relevant literature.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618637","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":"Characterization of Pediatric Acute Myeloid Leukemia With t(7;12)(q36;p13)","authors":"Anders Östlund,&nbsp;Ahmed Waraky,&nbsp;Anna Staffas,&nbsp;Helene Sjögren,&nbsp;Barbara De Moerloose,&nbsp;Nira Arad-Cohen,&nbsp;Daniel Cheuk,&nbsp;Jose Maria Fernandez Navarro,&nbsp;Kirsi Jahnukainen,&nbsp;Gertjan J. L. Kaspers,&nbsp;Zhanna Kovalova,&nbsp;Ramune Pasauliene,&nbsp;Kadri Saks,&nbsp;Bernward Zeller,&nbsp;Ulrika Norén-Nyström,&nbsp;Henrik Hasle,&nbsp;Linda Fogelstrand,&nbsp;Jonas Abrahamsson,&nbsp;Lars Palmqvist","doi":"10.1002/gcc.70003","DOIUrl":"10.1002/gcc.70003","url":null,"abstract":"<p>Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is a recurrent translocation in AML in infants or very young children and was recently included in the World Health Organization (WHO) Classification of Hematolymphoid Tumors. AML with t(7;12) is reported to involve <i>MNX1</i> and <i>ETV6</i> signaling; however, the mechanism of leukemogenesis is not well understood, and the presence of <i>MNX1</i>::<i>ETV6</i> fusion transcripts has only been confirmed in approximately 50% of cases. In contrast, high expression of <i>MNX1</i> has been seen in all investigated cases. In this study, we investigated the clinical as well as biological characteristics of 12 pediatric AML with t(7;12) and performed whole transcriptome (WTS) and whole genome sequencing (WGS) on six of these. There was no significant difference in event-free survival or overall survival of these t(7;12) AML patients compared with other AML in the same age group. Interestingly, WTS identified several fusion transcripts involving <i>ETV6</i> but not together with <i>MNX1</i>. WGS identified the genomic breakpoints and revealed that a common fusion partner on chromosome 7 was <i>NOM1</i>. Principal component analysis (PCA) of the WTS data showed that all t(7;12) AML cases cluster together, separate from all other pediatric AML subtypes; all cases had high expression of <i>MNX1</i>, <i>MNX1-AS1</i>, and <i>MNX1-AS2</i>. Hence, t(7;12) AML, despite expressing different fusion transcripts and with varying translocation breakpoints, constitutes a phenotypically homogenous subgroup. This underlines that the leukemia-driving event most likely is ectopic expression of <i>MNX1</i> and that this therefore should be the defining Classifying criteria of this type of AML.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604172","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":"Malignant Peripheral Nerve Sheath Tumor (MPNST) With Smooth Muscle Differentiation of the Uterus—A Case Report With Emphasis on Diagnostic Pitfalls and Value of DNA Methylation Analysis","authors":"Horace M. H. Cheung,&nbsp;Anthony P. Y. Liu,&nbsp;Maximus C. F. Yeung","doi":"10.1002/gcc.70006","DOIUrl":"10.1002/gcc.70006","url":null,"abstract":"<div>\u0000 \u0000 <p>With no more than two dozen cases reported in the literature, malignant peripheral nerve sheath tumor (MPNST) is a rare primary mesenchymal neoplasm arising in the female genital tract. Most cases occurred in middle-aged adults with high grade histology, unfavorable clinical outcome, and no history of neurofibromatosis type 1. Its extreme rarity in this site no doubt poses a diagnostic challenge during routine clinical practice. In the following, we report an additional case of uterine MPNST occurring in a 49-year-old Chinese woman, which was initially misdiagnosed as a leiomyosarcoma. The primary tumor showed two distinctive components—a high-grade poorly differentiated component with markedly pleomorphic spindle cells arranged in a peritheliomatous pattern; and a leiomyosarcoma-like (LMS-like) component with tumor cells displaying obvious myoid differentiation. The patient suffered a recurrence less than 2 years later with the recurrent tumor demonstrating similar features to the high-grade component of the primary tumor. The patient eventually succumbed 46 months later after developing another recurrence despite receiving targeted therapy and chemotherapy. On retrospective molecular analysis, no clinically relevant fusion transcript was detected on RNA sequencing. Interestingly instead, DNA methylation analysis showed the tumor clustered with the “MPNST” group in the German Cancer Research Center (DKFZ) sarcoma classifier. The tumor was also found to have <i>EED</i> gene homozygous deletion, multiple copy number alterations and loss of H3K27me3 expression in both high-grade and LMS-like components. Combining histology with all the ancillary tests results, the diagnosis was most consistent with MPNST. Our case highlights the diagnostic pitfalls for MPNST arising in the female genital tract and the potential clinical utility of DNA methylation analysis.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604177","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":"Sporadic Breast Angiosarcoma With MYC Amplification on Extrachromosomal Circular DNA Detected Using Nanopore Sequencing in an Adolescent Female","authors":"Naohiro Makise,&nbsp;Jason Lin,&nbsp;Hajime Kageyama,&nbsp;Mariko Oikawa,&nbsp;Takahiro Sugiyama,&nbsp;Hidetada Kawana,&nbsp;Akinobu Araki,&nbsp;Shouko Hayama,&nbsp;Rikiya Nakamura,&nbsp;Hideyuki Kinoshita,&nbsp;Hiroto Kamoda,&nbsp;Yoko Hagiwara,&nbsp;Tsukasa Yonemoto,&nbsp;Masahito Kawazu,&nbsp;Makiko Itami","doi":"10.1002/gcc.70004","DOIUrl":"10.1002/gcc.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Angiosarcoma (AS) is a malignant vascular neoplasm comprising neoplastic endothelial cells accounting for 1%–4% of soft tissue sarcomas. While lymphedema-associated and post-irradiation ASs are almost always driven by a high-level amplification of <i>MYC</i> (8q24), sporadic ASs, including those of breast parenchymal origin, typically lack <i>MYC</i> amplification. Here, we report a case of sporadic breast <i>MYC</i>-amplified AS in a 19-year-old female with no history of lymphedema or irradiation, who was referred to our hospital for an enlarging right breast mass. After needle biopsy, the patient underwent right mastectomy and axillary lymphadenectomy. Microscopically, atypical endothelial cells proliferated and formed well-defined or slit-like vascular channels that invaded and dissected the breast parenchymal fat, ducts, and lobules. In a limited area, the tumor cells showed solid sheet-like proliferation with increased mitotic figures of 40 per 2 mm² with a small area of necrosis. Immunohistochemical analysis revealed strong positivity for c-Myc. Fluorescence in situ hybridization (FISH) with <i>MYC</i> break-apart probes showed a high-level 5′ single signal amplification. The patient was disease-free 16 months post-surgery. Nanopore sequencing successfully detected not only a high-level amplification of the 8q24 region, including <i>MYC</i>, but also multiple structural variants of the 8q24 region. In-depth analysis revealed extrachromosomal circular DNA amplification including the <i>MYC</i> protein-coding region and upstream region but not the downstream region. We also performed methylation classification using nanopore-based methylation data to successfully categorize the tumor as AS. This case report highlights the potential utility of nanopore sequencing in the diagnosis of sarcomas.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604187","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":"Microsatellite Instability and Loss of Heterozygosity as Prognostic Markers in Oral Squamous Cell Carcinoma: Molecular Mechanisms, Detection Techniques, and Therapeutic Strategies","authors":"Leyla Arslan Bozdag,&nbsp;Sevinç Inan,&nbsp;Sibel Elif Gultekin","doi":"10.1002/gcc.70002","DOIUrl":"10.1002/gcc.70002","url":null,"abstract":"<p>The aim of this study was to conduct a systematic review of research investigating the potential role of microsatellite instability (MSI) and loss of heterozygosity (LOH) in oral squamous cell carcinoma (OSCC), with a focus on molecular mechanisms, detection methods, and therapeutic approaches. Search for articles involved the PubMed and Scopus. Previous retrospective and prospective studies identified variations between oral cancers that exhibit microsatellite stability and LOH. In this search, 294 articles were initially retrieved. Of these, 70 were excluded due to duplication, 106 were identified as ineligible by automated tools, and 24 were excluded as they were published in languages other than English. An additional 94 articles were excluded, 32 of which focused on head and neck cancers broadly, and 8 could not be accessed due to withdrawal. Ultimately, a systematic review was conducted based on 54 selected articles. Among the chromosomes analyzed for MSI and LOH, the highest frequency of LOH was observed on chromosome 9p. The MSI subtype is particularly susceptible to immunotherapeutic methods, such as the use of anti-PD-L1 and anti-CTLA4 antibodies, owing to its strong immunogenicity and ubiquitous expression of immune checkpoint ligands. Given the distinct characteristics and clinical behavior of oral cancer with MSI compared to microsatellite stable disease, it is advisable to incorporate MSI testing into the diagnostic process for all stages of tumor development. This ensured that each patient had received precise and effective treatment.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521727","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":"Aggressive Spindle Cell Sarcoma in Young Woman With the FGFR1::EBF2 Fusion","authors":"Harumi Nakamura,&nbsp;Yoji Kukita,&nbsp;Ken-ichi Yoshida,&nbsp;Hironari Tamiya,&nbsp;Shigeki Kadonaga,&nbsp;Satoshi Takenaka,&nbsp;Toshinari Yagi","doi":"10.1002/gcc.70000","DOIUrl":"https://doi.org/10.1002/gcc.70000","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449222","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":"Cell Senescence and the Genetics of Melanoma Development","authors":"Sophie M. Constantinou,&nbsp;Dorothy C. Bennett","doi":"10.1002/gcc.23273","DOIUrl":"https://doi.org/10.1002/gcc.23273","url":null,"abstract":"<p>Cutaneous malignant melanoma is an aggressive skin cancer with an approximate lifetime risk of 1 in 38 in the UK. While exposure to ultraviolet radiation is a key environmental risk factor for melanoma, up to ~10% of patients report a family history of melanoma, and ~1% have a strong family history. The understanding of causal mutations in melanoma has been critical to the development of novel targeted therapies that have contributed to improved outcomes for late-stage patients. Here, we review current knowledge of the genes affected by familial melanoma mutations and their partial overlap with driver genes commonly mutated in sporadic melanoma development. One theme linking a set of susceptibility loci/genes is the regulation of skin pigmentation and suntanning. The largest functional set of susceptibility variants, typically with high penetrance, includes <i>CDKN2A</i>, <i>RB1</i>, and telomerase reverse transcriptase (<i>TERT</i>) mutations, associated with attenuation of cell senescence. We discuss the mechanisms of action of these gene sets in the biology and progression of nevi and melanoma.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449221","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":"Sporadic NF1-Mutated Inflammatory Polyps of the Colon: A Case Report and Brief Literature Review","authors":"Azfar Neyaz,&nbsp;Ibrahim Abukhiran,&nbsp;Rana Naous","doi":"10.1002/gcc.70001","DOIUrl":"https://doi.org/10.1002/gcc.70001","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451212","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}