Cancer Genomics & Proteomics最新文献

{"title":"Engineered Methioninase-expressing Tumor-targeting <i>Salmonella typhimurium</i> A1-R Inhibits Syngeneic-Cancer Mouse Models by Depleting Tumor Methionine.","authors":"Yutaro Kubota, Ming Zhao, Qinghong Han, Yusuke Aoki, Noriyuki Masaki, Koya Obara, Sei Morinaga, Kohei Mizuta, Motokazu Sato, Michael Bouvet, Koichi Kubota, Takuya Tsunoda, Robert M Hoffman","doi":"10.21873/cgp.20499","DOIUrl":"10.21873/cgp.20499","url":null,"abstract":"<p><strong>Background/aim: </strong>We previously developed <i>Salmonella typhimurium</i> A1-R, which selectively targets and kills tumors. In the present study, we established recombinant methioninase (rMETase)-producing <i>Salmonella typhimurium</i> A1-R (A1-R-rMETase), by transfer of the <i>Pseudomonas putida methioninase</i> gene, to target methionine addiction of syngeneic-cancer mouse models.</p><p><strong>Materials and methods: </strong>A plasmid containing the <i>Pseudomonas putida methioninase</i> gene was extracted from METase-producing recombinant <i>E. coli</i> and inserted into <i>Salmonella typhimurium</i> A1-R using electroporation. Lewis Lung Carcinoma (LLC) cells (10⁶) were injected subcutaneously in male C57BL/6 mice aged 4-6 weeks. We determined that 10⁸ <i>Salmonella typhimurium</i> A1-R-rMETase administered iv was a safe dosage in C57BL/6 mice and was used for efficacy studies on LLC tumors in C57BL/6 mice. Tumor size was measured with calipers three times per week for 3 weeks. On day 22, tumor methionine levels were measured using HPLC in the control mice injected with phosphate-buffered saline (PBS) and the mice injected with <i>Salmonella typhimurium</i> A1-R-rMETase.</p><p><strong>Results: </strong>The mean LLC tumor size of each group on day 22 was as follows: PBS control: 741.5 mm³; mice injected with <i>Salmonella typhimurium</i> A1-R: 566.3 mm³ (<i>p</i>=0.370); and mice injected with <i>Salmonella typhimurium</i> A1-R-rMETase: 198.8 mm³ (<i>p</i>=0.0003 <i>vs</i> control and <i>p</i>=0.0117 <i>vs. Salmonella</i> A1-R). The mice injected with <i>Salmonella typhimurium</i> A1-R-rMETase showed a significantly lower mean tumor methionine level than mice injected with PBS (5.9 nM/mg protein <i>vs</i> 11.1 nM/mg protein, <i>p</i>=0.0095). <i>Salmonella typhimurium</i> A1-R-rMETase grew continuously in the tumors but not in the liver or spleen.</p><p><strong>Conclusion: </strong>Tumor-targeting <i>Salmonella typhimurium</i> A1-R engineered to express the <i>Pseudomonas putida methioninase</i> gene, inhibited LLC tumor growth in a syngeneic mouse model and reduced the methionine level in the tumor. <i>Salmonella typhimurium</i> A1-R-rMETase combines the tumor targeting and killing capability of <i>Salmonella typhimurium</i> A1-R plus rMETase which targets the methionine addiction of cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"247-257"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEFA1, Primarily Expressed at the Invasive Tumor Front, Promotes OSCC Cell Invasion and Tumor Growth.","authors":"Hojin Jeong, Sang Woong Park, Young Sun Hwang","doi":"10.21873/cgp.20504","DOIUrl":"10.21873/cgp.20504","url":null,"abstract":"<p><strong>Background/aim: </strong>The tumor microenvironment greatly influences cancer occurrence, progression, and treatment resistance, making it a key target alongside cancer cells. In squamous cell carcinoma, the invasive front is crucial for studying invasion mechanisms driven by the surrounding microenvironment and for identifying biomarkers to diagnose and predict invasive cancer. In this study, we aimed to elucidate the regulation of cancer characteristics through the interactions between factors at the invasive tumor front and the surrounding tumor microenvironment.</p><p><strong>Materials and methods: </strong>The invasive tumor front (ITF) and tumor center (TC) of collective cancer invasion were analyzed using microarray to compare gene expression. A stable cell line with depleted DEFA1 expression was established, and its effect on cancer growth was observed using a mouse tongue xenograft model. Invasive activity was assessed using Transwell assays. Gene profiling of cancer cells and analysis of secreted proteins interacting with U937 monocytic cells during co-culture were conducted using QuantSeq 3' mRNA sequencing and LC-MS/MS analysis.</p><p><strong>Results: </strong>DEFA1 was overexpressed at the ITF of collective cancer invasion. YD10B cells with depleted DEFA1 expression exhibited significantly reduced invasiveness and tumor growth without changes in the cell cycle distribution. Co-culture with U937 cells significantly enhanced the invasiveness of YD10B cells, which was inhibited by anti-DEFA1 treatment. QuantSeq 3' mRNA sequencing and LC-MS/MS analyses confirmed that DEFA1 derived from U937 cells increased the invasiveness of YD10B cells. Recombinant DEFA1 (rDEFA1) significantly enhanced the invasiveness of YD10B cells <i>via</i> the JNK MAPK/NF-[Formula: see text]B signaling pathway, independent of changes in DEFA1 expression within YD10B cells.</p><p><strong>Conclusion: </strong>DEFA1 is crucial for cancer invasion and growth, and monocyte-derived DEFA1 exacerbates these traits. This study highlights DEFA1's role in promoting invasion at the tumor front, where interactions with the microenvironment are active.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"326-345"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 E-cadherin Activates EGFR-MEK/ERK Signaling, Promoting Cervical Cancer Progression.","authors":"Hee Yun, Gwan Hee Han, Daniel J Wee, Doo-Byung Chay, Joon-Yong Chung, Jae-Hoon Kim, Hanbyoul Cho","doi":"10.21873/cgp.20501","DOIUrl":"10.21873/cgp.20501","url":null,"abstract":"<p><strong>Background/aim: </strong>This study investigated the relationship between E-cadherin down-regulation and enhanced pERK1/2 signaling in cervical cancer, evaluated their combined prognostic impact, and explored potential therapeutic targets.</p><p><strong>Materials and methods: </strong>We analyzed 188 cervical cancer specimens and 300 normal cervical tissue samples using tissue microarray and immunohistochemistry. Small interfering RNA transfection and western blotting were used to study molecular interactions in cervical cancer cell lines.</p><p><strong>Results: </strong>We observed a significant inverse correlation between E-cadherin and pERK1/2 expression, as well as poor disease-free survival and overall survival. Additionally, molecular analysis indicated that E-cadherin silencing enhanced ERK signaling and promoted cancer cell proliferation.</p><p><strong>Conclusion: </strong>The findings suggest that E-cadherin and pERK1/2 are crucial biomarkers for cervical cancer prognosis and their interaction provides a potential target for therapeutic interventions. Further studies are recommended to explore these pathways in the clinical setting.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 2","pages":"271-284"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of HMGB1 Expression as a Clinical Biomarker for Cholangiocarcinoma.","authors":"Supakan Amontailak, Attapol Titapun, Apinya Jusakul, Raynoo Thanan, Phongsaran Kimawaha, Wassana Jamnongkan, Malinee Thanee, Papitchaya Sirithawat, Songpol Haohan, Anchalee Techasen","doi":"10.21873/cgp.20489","DOIUrl":"10.21873/cgp.20489","url":null,"abstract":"<p><strong>Background/aim: </strong>Cholangiocarcinoma (CCA) is an epithelial malignancy that is most prevalent in Southeast Asia, particularly in the northeast of Thailand. Identifying and establishing specific biomarkers of CCA is crucial for ensuring accurate prognosis and enabling effective treatment. High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that can be released by dead or injured cells and is associated with tumor progression. This study aimed to investigate the expression levels of HMGB1 in CCA.</p><p><strong>Materials and methods: </strong>The clinical significance of HMGB1 levels was assessed by examining their correlation with patients' clinicopathological data. A bioinformatics analysis was conducted to examine HMGB1 mRNA expression and perform survival analysis. The expression levels of 137 tissue cases were evaluated using the immunohistochemical technique, whereas the serum levels of 31 cases were evaluated using indirect ELISA.</p><p><strong>Results: </strong>The GEPIA analysis demonstrated that HMGB1 exhibited elevated mRNA expression in CCA compared to the normal group. Immunohistochemical staining revealed that HMGB1 expression was primarily localized in the nucleus. High HMGB1 expression was observed in 57.6% of tissue samples, while low expression was detected in 42.4%. There was a significant positive correlation between high HMGB1 expression and the extrahepatic type of CCA as well as lymph node metastasis. The measurement of HMGB1 levels were assessed using indirect ELISA in 31 CCA serum samples, where 51.6% exhibited elevated concentrations of HMGB1. Elevated serum HMGB1 levels were significantly associated with advanced tumor stages and high levels of bilirubin levels.</p><p><strong>Conclusion: </strong>HMGB1 in both tissue biopsies and blood serum shows potential as a predictive biomarker in CCA patients. These biomarkers could form the basis for facilitating more effective treatment planning.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"81-89"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation and Function of CCL2 and N-Myc in Retinoic Acid-treated Neuroblastoma Cells.","authors":"Nanke Murra, Nina Sophie Pommert, Berit Schmidt, Reema Sami Issa, Meike Kaehler, Henrike Bruckmueller, Vera Tim, Ingolf Cascorbi, Vicki Waetzig","doi":"10.21873/cgp.20490","DOIUrl":"10.21873/cgp.20490","url":null,"abstract":"<p><strong>Background/aim: </strong>Treatment with retinoic acid (RA) often promotes neuroblastoma differentiation and growth inhibition, including the suppression of the expression of the MYCN oncogene. However, RA also targets protumoral chemokines, such as CCL2, which may contribute to the development of resistance. The present study aimed to investigate the regulation and function of CCL2 and N-Myc in RA-treated neuroblastoma cells.</p><p><strong>Materials and methods: </strong>In Kelly or SH-SY5Y cells, viability was quantified by cell fitness assays. Expression was analyzed using quantitative PCR and the regulation of proteins using enzyme-linked immunoabsorbent assays (ELISA) or western blots.</p><p><strong>Results: </strong>In MYCN-amplified Kelly cells, endogenous CCL2 levels were significantly lower compared to MYCN non-amplified SH-SY5Y cells. Treatment with 5 μM RA increased CCL2 release in both cell lines, but reduced N-Myc levels and cell numbers in Kelly cells. Over-expression of MYCN enhanced viability in SH-SY5Y cells, but did not affect RA-induced CCL2 release, while supplementation of CCL2 in Kelly cells did not prevent RA-mediated growth reduction. Impaired N-Myc or CCL2 signaling reduced the survival of all RA-treated cells and inhibition of N-Myc also decreased CCL2 levels. However, attenuated survival signaling was not generally associated with reduced levels of N-Myc or CCL2. Co-application of RA and the growth factor receptor inhibitors cediranib or crizotinib decreased N-Myc levels only in Kelly cells, while CCL2 release was dependent on the cell type and stimulus.</p><p><strong>Conclusion: </strong>CCL2 and N-Myc promote the viability of RA-treated cells, although the levels of these mediators were not consistently correlated with cellular outcomes, especially during apoptotic signaling.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"90-102"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RFC3 Knockdown Decreases Cervical Cancer Cell Proliferation, Migration and Invasion.","authors":"Jae Woong Koh, Seon-Joo Park","doi":"10.21873/cgp.20493","DOIUrl":"10.21873/cgp.20493","url":null,"abstract":"<p><strong>Background/aim: </strong>Replication factor C subunit 3 (RFC3) is a critical component of the replication factor C complex, which is essential for DNA replication and repair. Recent studies have highlighted the RFC3's significance in various cancer types. Herein, we aimed to elucidate its biological role in cervical cancer.</p><p><strong>Materials and methods: </strong>Cervical cancer cells were transfected with RFC3 or control siRNA. Cell viability was assessed using the MTT assay over a 4-day period and its clonogenic potential was determined using colony formation assays. Flow cytometry analysis was performed to evaluate cell cycle distribution. Transwell migration and invasion assays were performed to assess the migration and invasion abilities of cervical cancer cells.</p><p><strong>Results: </strong>RFC3 knockdown significantly inhibited cell proliferation, induced cell-cycle arrest, and decreased migration and invasion in HeLa and ME-180 cells compared to control siRNA-transfected cells.</p><p><strong>Conclusion: </strong>The crucial role of RFC3 in cervical cancer progression is highlighted. RFC3 knockdown resulted in decreased cervical cancer cell proliferation, migration and invasion, suggesting its potential as a therapeutic target in cervical cancer.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"127-135"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FN1 and VEGFA Are Potential Therapeutic Targets in Glioblastoma as Determined by Bioinformatics Analysis.","authors":"Mijung Im, Jungwook Roh, Wonyi Jang, Wanyeon Kim","doi":"10.21873/cgp.20488","DOIUrl":"10.21873/cgp.20488","url":null,"abstract":"<p><strong>Background/aim: </strong>Glioblastoma is the most malignant brain tumor, and despite advances in treatment, survival rates are still dismal. Therefore, a comprehensive understanding of the underlying molecular mechanisms of glioblastoma is needed. This study suggests potential therapeutic targets in glioblastoma that may provide new therapeutic insights.</p><p><strong>Materials and methods: </strong>To identify hub genes in glioblastoma, three datasets were selected from the GEO database. After screening DEGs using GEO2R, GO and KEGG analyses were performed using DAVID. The PPI network was visualized using Cytoscape and 7 hub genes were extracted. The prognostic potential of 7 hub genes was investigated using the Gliovis and GEPIA2 databases.</p><p><strong>Results: </strong>In total, 176 up-regulated and 263 down-regulated genes were identified. From the PPI network, 7 hub genes were identified including CAMK2A, DLG4, SNAP25, SYT1, MYC, FN1, and VEGFA. Out of the 7 hub genes identified, FN1 and VEGFA have been associated with a poor prognosis in glioblastoma based on the survival analysis.</p><p><strong>Conclusion: </strong>This study suggests that high levels of FN1 and VEGFA expression are associated with a poor prognosis in glioblastoma and that both genes are promising targets for glioblastoma therapy. Bioinformatics analysis of DEGs revealed putative targets that might reveal the molecular mechanisms underlying glioblastoma.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"70-80"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>FAM32A</i> Suppression Decreases 5-Fluorouracil-induced Apoptosis and Is Associated With Poor Prognosis in Gastric Cancer.","authors":"Yuya Agatsuma, Dai Shimizu, Shinichi Umeda, Haruyoshi Tanaka, Norifumi Hattori, Masamichi Hayashi, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Michitaka Fujiwara, Yasuhiro Kodera","doi":"10.21873/cgp.20487","DOIUrl":"10.21873/cgp.20487","url":null,"abstract":"<p><strong>Background/aim: </strong>The development of new biomarkers to predict cancer patient prognosis is expected to aid in treatment selection, contributing to improved outcomes. In this study, we extracted a candidate gene associated with patient prognosis from a public database and investigated the molecular and biological functions and clinical significance of the gene in gastric cancer.</p><p><strong>Materials and methods: </strong>We analyzed The Cancer Genome Atlas database and identified the family with sequence similarity 32 member a (FAM32A) as a candidate gene. We investigated the clinicopathological significance of FAM32A mRNA and protein expression in 300 and 176 gastric cancer patients respectively. We evaluated the molecular and biological functions by suppressing FAM32A expression in gastric cancer cell lines using small interfering RNA.</p><p><strong>Results: </strong>In the polymerase chain reaction (PCR) cohort, low FAM32A expression group showed significantly shorter disease-specific survival (DSS) [hazard ratio (HR)=1.586; 95% confidence interval (95% CI)=1.056-2.382, p=0.026]. In the immunohistochemistry cohort, the FAM32A(-) group had significantly shorter overall survival (HR=1.703; 95% CI=1.050-2.764, p=0.031) and DSS (HR=2.123; 95% CI=1.185-3.804, p=0.011). Multivariate Cox hazard analysis revealed that FAM32A(-) was an independent adverse prognostic factor for DSS (p<0.001). AGS cell lines with FAM32A knockdown exhibited significant resistance to 5-fluorouracil (5-FU) and reduced apoptosis upon 5-FU administration. Gene set enrichment analysis indicated decreased gene expression related to the p53 signaling pathway in AGS cells with FAM32A knockdown that were treated with 5-FU.</p><p><strong>Conclusion: </strong>FAM32A suppression decreases 5-FU-induced apoptosis. Low FAM32A expression is associated with a poor prognosis in gastric cancer, suggesting its potential as a biomarker.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"55-69"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Different <i>NF1</i> Pathogenic Variants in a Family With Neurofibromatosis Type 1.","authors":"Tabea I Hartung, Lan Kluwe, Reinhard E Friedrich, Said C Farschtschi","doi":"10.21873/cgp.20485","DOIUrl":"10.21873/cgp.20485","url":null,"abstract":"<p><strong>Background/aim: </strong>Neurofibromatosis type 1 (NF1) is a genetic disorder with an incidence of approximately one in 3,000. More than half of the patients have new de novo pathogenic variants of the NF1 gene. In most family cases, all family members share an identical NF1-variant. The aim of the study was to investigate the very rare phenomenon of de novo variants in cases of familial neurofibromatosis type 1 and highlight its implications for genetic testing and counseling.</p><p><strong>Patients and methods: </strong>Patients underwent clinical examination in our NF outpatient clinic and genetic testing for the NF1-gene was performed by targeted sequencing. All family members were profiled by short-tandem repeat marker analysis. Additionally, a probability calculation was performed for this extremely rare event.</p><p><strong>Results: </strong>In one NF1 family consisting of mother, father, and two sons, two different pathogenic variants of the NF1 gene were found. The father and one son share one NF1-variant and the other son carries a different de novo NF1-variant. Neither of these two NF1-variants was found in the unaffected mother. Short-tandem repeat analysis confirmed the paternity and revealed that the two sons inherited two different NF1-alleles from their father. The probability of two different NF1-variants occurring in one family is calculated as 1:9,000,000.</p><p><strong>Conclusion: </strong>Two different NF1-variants in one family is an extremely rare phenomenon: yet its occurrence is not impossible and therefore should be considered in genetic diagnosis and counselling. For an offspring with the indication for neurofibromatosis type 1, but lacking the familial pathogenic variant, a screening of the whole NF1-gene is necessary to detect potential new pathogenic variants and for exact diagnosis.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"41-45"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Genetic Evolution and Treatment Challenges in Myeloid Neoplasms: A Case of Persistent t(2;3)(p15~23;q26)/<i>MECOM</i> Rearrangement, <i>SF3B1</i> Mutation, and Transient <i>TNIP1::PDGFRB</i> Chimera.","authors":"Kristin Andersen, Geir E Tjønnfjord, Malu Lian Hestdalen, Signe Spetalen, Ioannis Panagopoulos","doi":"10.21873/cgp.20483","DOIUrl":"10.21873/cgp.20483","url":null,"abstract":"<p><strong>Background/aim: </strong>Myelodysplastic syndromes (MDSs) are clonal bone marrow disorders characterized by ineffective hematopoiesis. They are classified based on morphology and genetic alterations, with SF3B1 variants linked to favorable prognosis and MECOM rearrangements associated with poor outcomes. The combined effects of these alterations remain unclear. We report an MDS patient carrying both SF3B1 and MECOM alterations who developed transient eosinophilia accompanied by a TNIP1::PDGFRB chimera in a subset of MECOM-affected cells.</p><p><strong>Case report: </strong>A 73-year-old woman was diagnosed with myeloid neoplasia with excess blasts and multilineage dysplasia (MDS-EB1). Six months later, SF3B1 mutations were identified, leading to a diagnosis of MDS-SF3B1. Despite azacitidine treatment, her condition worsened, showing hypercellular bone marrow and eosinophilia. Genetic analysis revealed a t(2;3)(p15~23;q26)/MECOM rearrangement and TNIP1::PDGFRB chimera. Imatinib eradicated eosinophilia and reduced TNIP1::PDGFRB-positive cells, but the MECOM-clone persisted. Subsequent treatments, including hydroxyurea, mercaptopurine, and low-dose cytarabine, were ineffective. FLT3 mutations and high EVI1 transcript levels were later detected. The patient succumbed to progressive disease.</p><p><strong>Conclusion: </strong>This case highlights the complexity of MDS and the importance of genetic abnormalities in treatment planning. Persistent MECOM rearrangement and the TNIP1::PDGFRB chimera emphasize the need for further research into resistance mechanisms.</p>","PeriodicalId":9516,"journal":{"name":"Cancer Genomics & Proteomics","volume":"22 1","pages":"24-33"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}