Genes, Chromosomes & Cancer最新文献

{"title":"Aberrant Energy Metabolism in Tumors and Potential Therapeutic Targets","authors":"Shuhao Fan,&nbsp;Jianhua Guo,&nbsp;Hui Nie,&nbsp;Huabao Xiong,&nbsp;Yong Xia","doi":"10.1002/gcc.70008","DOIUrl":"https://doi.org/10.1002/gcc.70008","url":null,"abstract":"<p>Energy metabolic reprogramming is frequently observed during tumor progression as tumor cells necessitate adequate energy production for rapid proliferation. Although current medical research shows promising prospects in studying the characteristics of tumor energy metabolism and developing anti-tumor drugs targeting energy metabolism, there is a lack of systematic compendiums and comprehensive reviews in this field. The objective of this study is to conduct a systematic review on the characteristics of tumor cells' energy metabolism, with a specific focus on comparing abnormalities between tumor and normal cells, as well as summarizing potential targets for tumor therapy. Additionally, this review also elucidates the aberrant mechanisms underlying four major energy metabolic pathways (glucose, lipid, glutamine, and mitochondria-dependent) during carcinogenesis and tumor progression. Through the utilization of graphical representations, we have identified anomalies in crucial energy metabolism pathways, encompassing transporter proteins (glucose transporter, CD36, and ASCT2), signaling molecules (Ras, AMPK, and PTEN), as well as transcription factors (Myc, HIF-1α, CREB-1, and p53). The key molecules responsible for aberrant energy metabolism in tumors may serve as potential targets for cancer therapy. Therefore, this review provides an overview of the distinct energy-generating pathways within tumor cells, laying the groundwork for developing innovative strategies for precise cancer treatment.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708377","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":"Peter Besmer, PhD Obituary (1940–2024)","authors":"Cristina Antonescu","doi":"10.1002/gcc.70014","DOIUrl":"https://doi.org/10.1002/gcc.70014","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708339","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":"Fibromyxoid aSoft Tissue Tumor With PLAG1 Fusion—The First Case in an Adult Patient","authors":"M. Strnadová,&nbsp;J. Balko,&nbsp;P. Brož,&nbsp;L. Wagenknecht,&nbsp;L. Krsková","doi":"10.1002/gcc.70011","DOIUrl":"10.1002/gcc.70011","url":null,"abstract":"<p>With the expanding possibilities of human genome research in recent years, the number of cases of soft tissue tumors that we are able to classify into the correct subgroups and to reveal their molecular profile is increasing. Among such tumors, we can also consider neoplasms that have a specific fusion of genes, in our case namely the pleomorphic adenoma gene 1 (<i>PLAG1)</i> and its partner. <i>PLAG1</i> gene fusions were previously associated mainly with salivary gland pleomorphic adenomas, lipoblastomas, myoepithelial tumors, uterine epitheloid, myxoid leiomyosarcomas, and, recently, with PLAG1-rearranged fibromyxoid soft tissue tumors. To our knowledge, we report the first case of a soft tissue tumor with a <i>PLAG1</i> fusion gene in an adult. In our case, we detected a new <i>H3-3B::PLAG1</i> fusion in a soft tissue tumor, which originally appeared as nodular fasciitis.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686796","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":"An Inflammatory Myofibroblastic Tumor With a Novel ALKV1180L Mutation Leading to Acquired Resistance to Tyrosine Kinase Inhibitors","authors":"Brittney Sharpe,&nbsp;Donald C. Green,&nbsp;Laura J. Tafe,&nbsp;Garrett T. Wasp,&nbsp;Darcy A. Kerr,&nbsp;Nooshin K. Dashti","doi":"10.1002/gcc.70012","DOIUrl":"10.1002/gcc.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that can locally recur and potentially metastasize. Approximately 50% of IMTs harbor rearrangements in the gene encoding anaplastic lymphoma kinase (<i>ALK</i>), a receptor tyrosine kinase that can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). With successful application of TKI in ALK-positive nonsmall cell carcinoma (NSCLC), ALK inhibitors are often first-line treatments for patients with unresectable or metastatic IMTs. Although acquired resistance to these agents may develop, resistance mechanisms are sparsely reported for IMTs. Here we report a case of a 71 year-old man with metastatic pulmonary IMT harboring a <i>DCTN1::ALK</i> fusion that progressed during alectinib TKI treatment. Whole exome sequencing of an enlarging metastatic lesion in right 4th rib revealed a novel p.V1180L mutation in the <i>ALK</i> tyrosine kinase domain as the mechanism of acquired resistance. To our knowledge, this is the first report of acquired p. V1180L mutation in IMTs treated with TKIs. In cases of ALK-positive IMTs that progress on TKI therapy, targeted sequencing for acquired <i>ALK</i> mutations may inform clinical decisions to adopt second-line therapeutic strategies.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675626","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":"Novel HMGA2::COL14A1 Fusion Identified in Xanthogranulomatous Epithelial Tumor/Keratin-Positive Giant Cell Tumor","authors":"Carina A. Dehner,&nbsp;Darya Buehler,&nbsp;Christopher Hofich,&nbsp;Kevin C. Halling,&nbsp;Andrew L. Folpe","doi":"10.1002/gcc.70010","DOIUrl":"10.1002/gcc.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Xanthogranulomatous epithelial tumor (XGET)/Keratin-positive giant cell tumor (KP-GCT) represents a spectrum of recently described neoplasms characterized by a proliferation of distinctive mononuclear cells expressing keratin within a background of osteoclast-like giant cells, mixed inflammatory cells, and a variably prominent xanthogranulomatous component. Recent studies demonstrated a recurrent <i>HMGA2::NCOR2</i> fusion in many cases. We herein describe a case of XGET/KP-GCT arising in the right femoral head of a 19-year-old male harboring a rare novel <i>HMGA2::COL14A1</i> fusion.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647332","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":"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}