Cancer Genetics最新文献

{"title":"TRIM29 promotes glioblastoma progression via ubiquitinating NEFL and activating the PI3K/AKT signaling pathway","authors":"Yuankun Liu ,&nbsp;Qisheng He ,&nbsp;Lingjie Zhu ,&nbsp;Mengmeng Zhong ,&nbsp;Hao Zhuang ,&nbsp;Ning Zhao ,&nbsp;Yijin Cai ,&nbsp;Chao Cheng ,&nbsp;Junfei Shao","doi":"10.1016/j.cancergen.2025.06.008","DOIUrl":"10.1016/j.cancergen.2025.06.008","url":null,"abstract":"<div><div>Tripartite motif-containing protein 29 (TRIM29) is a regulator of tumor progression across multiple cancer types. However, its functional significance in glioblastoma (GBM) remains poorly defined. In this study, we investigated the biological roles of TRIM29 in GBM and elucidated its underlying molecular mechanisms. Clinically, TRIM29 expression was significantly upregulated in glioma tissues compared to adjacent normal brain tissues, and elevated TRIM29 levels correlated with unfavorable prognosis in GBM patients. Functionally, both in vitro (GBM cell lines) and in vivo (a mouse xenograft model) experiments demonstrated that TRIM29 overexpression robustly enhanced GBM cell proliferation, migration, and invasive capacity. Mechanistically, TRIM29 directly interacted with neurofilament light polypeptide (NEFL), triggering K48-linked polyubiquitination and subsequent proteasomal degradation of NEFL[1]. This ubiquitination-dependent NEFL downregulation led to constitutive activation of the PI3K/AKT signaling pathway. Our findings uncover a novel TRIM29-NEFL-PI3K/AKT axis that drives glioblastoma malignancy, highlighting the therapeutic potential of targeting this pathway for GBM treatment.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 88-99"},"PeriodicalIF":1.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing germline mutational profile and its clinicopathological associations in Triple Negative Breast Cancer","authors":"Jisha John ,&nbsp;Ashwini Bapat ,&nbsp;Siddharth Gahlaut ,&nbsp;Naveen Luke ,&nbsp;Rahul Kumar ,&nbsp;Yashaswi Thakur ,&nbsp;Christina Mathew ,&nbsp;Aishwarya Konnur ,&nbsp;Namrata Namewar ,&nbsp;Ruhi Reddy ,&nbsp;Sanket Nagarkar ,&nbsp;Smeeta Nare ,&nbsp;George Thomas ,&nbsp;Laleh Busheri ,&nbsp;Asha Reddy ,&nbsp;Devaki Kelkar ,&nbsp;Santosh Dixit ,&nbsp;Chetan Deshmukh ,&nbsp;Ashraf ul Mannan ,&nbsp;Radhakrishnan Sabarinathan ,&nbsp;Chaitanyanand B Koppiker","doi":"10.1016/j.cancergen.2025.06.004","DOIUrl":"10.1016/j.cancergen.2025.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is the most common cancer in Indian women with a high incidence of triple negative breast cancer (TNBC). The high TNBC prevalence (&gt;25 %) in India remains a challenge in clinical management. Association of germline BRCA1/2 mutations in TNBCs is well-established as a predisposing factor for hereditary breast cancer risk. These studies are, however, predominantly representative of western population. Therefore, we investigated germline profiles of multi-institutional cohort of TNBC patients in India</div></div><div><h3>Methods</h3><div>Multigene NGS (next-generation sequencing) panel testing of Triple Negative Breast Cancer patients was conducted. All patients were offered pre-test and post-test counseling.</div></div><div><h3>Results</h3><div>In our study cohort of 192 TNBC patients, median age at diagnosis was 47 years (23–78). Germline pathogenic mutations were identified in 28.6 % cases. Of the 58 pathogenic mutations identified, <em>BRCA1</em> accounted for 72.4 % and <em>BRCA2</em> for 13.8 %. Eight pathogenic mutations were identified in non-BRCA genes associated with DNA damage response pathway. Ten novel mutations were identified in 3 genes namely <em>BRCA1, BRCA2</em> and <em>PALB2</em>. Comparison of allele-frequency with the global databases like TCGA (The Cancer Genome Atlas), gnomAD and Genome Asia 100 K indicated that the novel mutations were unique.</div></div><div><h3>Conclusions</h3><div>Our study confirms the major proportion of mutations in <em>BRCA1/2</em> genes in TNBCs in India. Interestingly, a higher proportion of VUS were found in the non-BRCA genes compared to BRCA1/2 emphasizing the need for functional studies of the non-BRCA genes. Large scale studies are warranted to elucidate the landscape of germline mutations relevant to the Indian population and their probable clinical implications.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 65-75"},"PeriodicalIF":1.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SATB2 plays a critical role in pancreatic cancer cell proliferation, migration and T cell cytotoxicity","authors":"Guixing Jiang ,&nbsp;Xinyang Zhou ,&nbsp;Shehuang Chen ,&nbsp;Faming Zhong ,&nbsp;Gaoshi Huang ,&nbsp;Bicheng Wu ,&nbsp;Qiaoyan Mou ,&nbsp;Gang Jiang ,&nbsp;Tianyu Lin","doi":"10.1016/j.cancergen.2025.06.006","DOIUrl":"10.1016/j.cancergen.2025.06.006","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to investigate the role played by special AT-rich sequence binding protein 2 (SATB2) in the immune system of pancreatic cancer (PC).</div></div><div><h3>Methods</h3><div>Expression of SATB2 was detected in online databases, PC cell lines, and PC tumor tissues. The correlation between SATB2 expression and immune cell infiltrations was examined. Cytotoxic activity of T lymphocytes to different PC cell lines was examined using CCK8. The constructed SATB2 overexpression and knockdown vectors were transformed into PC cell lines to detect T lymphocyte activity, cancer cell migration and proliferation levels. Finally, RNA-seq assay was performed on the overexpression and knockdown cell lines to screen for differentially expressed genes and performed qRT-PCR assay.</div></div><div><h3>Results</h3><div>Expression level of SATB2 in tumor tissues was significantly higher than that in normal tissues. SATB2 was associated with levels of multiple immune cells infiltration. SATB2 overexpression can inhibit the cytotoxicity of T lymphocytes in PC patients, promote the migration of PC cells, and increase the proportion of S-phase PC cells. There were 1,997 genes differentially expressed in PC cells after SATB2 overexpression and knockout, and these genes were participated in some immune processes, such as B cell chemotaxis and T cell differentiation.</div></div><div><h3>Conclusion</h3><div>SATB2 was highly expressed in PC and correlated with various levels of immune cell infiltration. SATB2 also inhibited the cytotoxicity of T cells and promoted PC cell migration. Altogether, SATB2 is recognized as a potential target for improving PC immunotherapy.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 53-64"},"PeriodicalIF":1.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the consistency of SMARCB1 variant classification and assertions of genotype-phenotype relationships in ClinVar","authors":"Samarth Satish ,&nbsp;Matan Bone ,&nbsp;Deborah Ritter ,&nbsp;Sharon E. Plon","doi":"10.1016/j.cancergen.2025.06.005","DOIUrl":"10.1016/j.cancergen.2025.06.005","url":null,"abstract":"<div><div>Pathogenic <em>SMARCB1</em> variants are associated with multiple Mendelian syndromes: Schwannomatosis (SM), Rhabdoid Tumour Predisposition Syndrome (RTPS1), and/or Coffin-Siris Syndrome (CSS). Although some data suggests genotype/phenotype relationships based on mutation type and location, this is not used consistently potentially due to inconsistent or absent phenotypic data. We used ClinVar, the largest public platform of variant classifications, to evaluate variant-specific data from clinical laboratories and cited publications to assess reporting consistency and genotype-phenotype relationships. When available, we extracted the mutation type, HGVS nomenclature, submitters, publications, and disease conditions. We compared the disease assertions made by laboratory submissions with those made in cited publications. Across 59 <em>SMARCB1</em> pathogenic variants, we identified 91 laboratory submissions (38 single and 20 multiple laboratories) and 40 cited articles. Of 91 submissions, 40 did not provide any disease assertion. Nonsense RTPS1 variants (<em>n</em> = 23) were mostly located in exon 2, with some in exons 1, 4 and 5, and other variant types were limited to frameshifts and large deletions/duplications. SM variants (<em>n</em> = 10) were found throughout <em>SMARCB1</em> with diverse variant types. CSS variants (<em>n</em> = 6) were single amino-acid deletions, missense and frameshift variants limited to exons 8 and 9. Although ClinVar is a rich source of variant data and extensively used during variant classification, the frequent absence of disease assertions and inconsistent reporting impedes implementation of clear genotype-phenotype relationships for <em>SMARCB1</em>. Given the significant clinical impact of these diagnoses a more standardized way of reporting pathogenic variants for diseases associated with multiple Mendelian disorders is needed.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 84-87"},"PeriodicalIF":1.4,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated m6A modification of pri-miR-93 promotes hepatocellular carcinoma progression via CDKN1A suppression","authors":"Yue Wang ,&nbsp;Xiaorong Zhang ,&nbsp;Fan Yang,&nbsp;Jiaqi Shang,&nbsp;Qing Yang","doi":"10.1016/j.cancergen.2025.06.003","DOIUrl":"10.1016/j.cancergen.2025.06.003","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) is the most common RNA modification in eukaryotic transcriptomes and plays a key role in various biological processes. However, its function in disease, particularly in microRNA regulation, remains unclear. Hepatocellular carcinoma (HCC) is a major global health challenge, with high morbidity and mortality rates. Investigating the role of m⁶A modification in HCC may provide valuable insights into its molecular mechanisms.</div><div>This study found that METTL3, an m⁶A methyltransferase, is significantly upregulated in HCC and is associated with poor prognosis. Bioinformatics analysis of the GSE37001 dataset showed that silencing METTL3 in HepG2 cells suppressed cell cycle-related pathways. Among several candidate miRNAs potentially regulated by METTL3 in an m⁶A-dependent manner, miR-93–5p was selected for further study. Experimental results demonstrated that METTL3-mediated m⁶A modification promotes miR-93–5p expression by facilitating pri-miR-93 processing. Functional assays confirmed that miR-93–5p directly targets CDKN1A and downregulates its expression. Moreover, METTL3 overexpression rescued the effects of METTL3 knockdown on pri-miR-93 m⁶A levels and miR-93–5p expression. Rescue experiments further showed that METTL3 promotes HCC cell proliferation and cell cycle progression while inhibiting apoptosis via the miR-93–5p/CDKN1A axis.</div><div>In summary, METTL3 is highly expressed in HCC and contributes to tumor progression by promoting miR-93–5p expression through m⁶A modification, thereby suppressing CDKN1A. These findings highlight a potential regulatory mechanism in HCC and suggest that targeting the METTL3/miR-93–5p/CDKN1A axis could be a novel therapeutic strategy.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 31-40"},"PeriodicalIF":1.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive molecular profiling in MOTION study","authors":"Olesya A. Kuznetsova ,&nbsp;Maxim V. Ivanov ,&nbsp;Alexandra A. Lebedeva ,&nbsp;Alexey A. Tryakin ,&nbsp;Egor M Veselovsky ,&nbsp;Maria S. Cheporova ,&nbsp;Fedor V. Moiseenko ,&nbsp;Margarita S. Gileva ,&nbsp;Alena I. Cherentsova ,&nbsp;Anna N. Tiatiushkina ,&nbsp;Mikhail Y. Fedyanin","doi":"10.1016/j.cancergen.2025.06.001","DOIUrl":"10.1016/j.cancergen.2025.06.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Comprehensive molecular profiling (CMP) and molecularly matched therapy (MMT) have uncertain roles in advanced solid tumors. This study evaluates CMP's real-world application in Russia.</div></div><div><h3>Methods</h3><div>A retrospective, multicenter study analyzed CMP data from 448 patients with advanced non-hematologic malignancies (2018–2024). Genomic alterations (GA) were classified by ESMO Scale for Clinical Actionability of molecular Targets (ESCAT).</div></div><div><h3>Results</h3><div>ESCAT tiers included I (15.4 %), II (4.9 %), III (31.5 %), IV (19.6 %), and V/X (28.6 %). Therapy data were available for 374 patients. MMT was recommended for 56.9 % but implemented in only 23.2 % (MMT group, <em>n</em> = 87). MMT group showed better objective response rate (61.3 % vs. 37.1 %, <em>p</em> = 0.001), disease control rate (24.0 % vs. 9.2 %, <em>p</em> = 0.003), and progression-free survival ratio (PFS 2/1) ≥ 1.3 (45.0 % vs. 16.2 %, <em>p</em> &lt; 0.01) compared to non-MMT group (<em>n</em> = 287). Median overall survival (OS) was borderline improved (12 vs. 8 months, HR 0.74, <em>p</em> = 0.06). Reasons for non-MMT management were low GA targetability (40 %), drug unavailability (30 %), clinical decline (23 %), and clinician preference (7 %). Patients with ≤3 prior therapies, ECOG performance status 0–1, and molecular tumor board discussion saw significant OS gains with MMT even for ESCAT III-V GA (5 vs. 18 months, HR 0.25, <em>p</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>MMT following CMP offers clinical benefit for selected patients, even with ESCAT III-V GA, underscoring its potential in personalized oncology.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 45-52"},"PeriodicalIF":1.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of pembrolizumab in MSI-high and BRCA-positive castration-resistant prostate cancer","authors":"Keita Higa ,&nbsp;Satoshi Yamamoto ,&nbsp;Koichiro Kurokawa ,&nbsp;Koki Watanabe ,&nbsp;Hiroki Bamba ,&nbsp;Sanji Kanaoka ,&nbsp;Kazuyoshi Nakamura","doi":"10.1016/j.cancergen.2025.06.002","DOIUrl":"10.1016/j.cancergen.2025.06.002","url":null,"abstract":"<div><div>This report presents a rare case of metastatic castration-resistant prostate cancer (CRPC) in an adult patient characterized by dual molecular alterations: microsatellite instability-high (MSI-H) and a BRCA2 mutation. Despite initial treatment with castration, Abiraterone, and sequential chemotherapy with docetaxel and cabazitaxel, the patient progressed to CRPC. Genetic testing revealed MSI-H and a BRCA2 mutation, prompting pembrolizumab therapy. The treatment led to a dramatic prostate-specific antigen (PSA) reduction .</div><div>This case underscores the importance of comprehensive genomic profiling for advanced prostate cancer. MSI-H tumors often respond to immune checkpoint inhibitors (ICIs) such as pembrolizumab, while BRCA2 mutations are associated with poly(ADP-ribose) polymerase inhibitors (PARPi) sensitivity. This dual alteration presents therapeutic challenges, as evidenced by pembrolizumab’s remarkable efficacy in this patient, highlighting its potential as a treatment option for MSI-H and BRCA-positive CRPC. Moreover, next-generation sequencing (NGS) played a crucial role in identifying actionable biomarkers not detected by earlier BRCA analyses, emphasizing the necessity of thorough genetic testing.</div><div>Further research is needed to optimize treatment strategies for cases with coexisting MSI-H and BRCA mutations, including exploring the synergistic effects of ICIs and PARP i. This case demonstrates the promise of pembrolizumab and advances the understanding of genetic testing’s role in tailoring therapies for complex molecular profiles in prostate cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 41-44"},"PeriodicalIF":1.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interplay of N6-Methyladenosine and Ferroptosis in Cancer: A Promising Therapeutic Avenue","authors":"Kirthik Roshan M ,&nbsp;Rituparna Pal ,&nbsp;Subhadra Kumari,&nbsp;Santosh Kumar,&nbsp;Srinivasan Muthuswamy","doi":"10.1016/j.cancergen.2025.05.007","DOIUrl":"10.1016/j.cancergen.2025.05.007","url":null,"abstract":"<div><div>Chemoresistance is an obstacle to the efficacy of chemotherapy in cancer. Numerous preclinical and clinical investigations have concentrated on mitigating drug resistance; nevertheless, chemoresistance remains a predominant challenge. Recent findings strongly suggest that ferroptosis, a form of non-apoptotic cell death characterized by lipid peroxidation, has been associated with resistance to cancer therapies, and the induction of ferroptosis has been shown to reverse drug resistance. The most common epitranscriptomic modification N6-methyladenosine (m6A) regulates cancer progression by enhancing the stability of oncogenes. Recent evidence suggests that dynamic m6A modifying factors play a role in chemosensitization by increasing the ferroptosis susceptibility. This review explores the mechanisms and significance of ferroptosis, including the role of m6A modifications in regulating ferroptosis-related genes. We discuss potential strategies for enhancing m6A-mediated ferroptosis to increase the effectiveness of chemotherapeutic treatments. Understanding the role of m6A modifications in regulating ferroptosis and their impact on the tumor cell response to chemotherapy could lead to identifying novel therapeutic targets, enhancing the effectiveness of chemotherapy and potentially overcoming chemoresistance.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 15-24"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute cardiac dysfunction in patients with ovarian cancer treated with Niraparib due to TFAM mutation: A case series and functional analysis","authors":"Fei Liu ,&nbsp;Wen Liu ,&nbsp;Danya Li ,&nbsp;Chunhua Tu ,&nbsp;Xiaoping Peng ,&nbsp;Yuan Wen","doi":"10.1016/j.cancergen.2025.05.006","DOIUrl":"10.1016/j.cancergen.2025.05.006","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is a leading cause of gynecological cancer mortality. Despite Niraparib's efficacy in increasing progression-free survival for recurrent ovarian cancer, its potential cardiotoxic effects are underexplored.</div></div><div><h3>Objective</h3><div>We performed a case series analysis involving two postmenopausal sisters who developed heart failure subsequent to Niraparib therapy for recurrent ovarian cancer.</div></div><div><h3>Methods</h3><div>Utilizing targeted next-generation sequencing (NGS), we identified a novel missense mutation c.98T&gt;A in Mitochondrial Transcription Factor A (<em>TFAM</em>) gene, which was subsequently confirmed by Sanger sequencing. To investigate the cardiotoxic effects of Niraparib, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC<img>CMs) carrying the identified mutation. The impact of the mutation on gene expression and protein levels was evaluated through real-time PCR and Western blot analyses.</div></div><div><h3>Results</h3><div>Two postmenopausal sisters treated with Niraparib suffered significant cardiac dysfunction. NGS identified a novel c.98T&gt;A variant in <em>TFAM</em> gene, resulting in a missense mutation. HEK293T cells transfected with mutant plasmids demonstrated normal expression of full-length <em>TFAM</em> mRNA and protein. hiPSC<img>CMs model revealed the variant alone did not induce cardiomyopathy. However, it predisposed to Niraparib-induced cardiomyopathy-like toxicity, mediated by metabolic dysregulation and increased cellular apoptosis</div></div><div><h3>Conclusion</h3><div>Our study revealed a novel <em>TFAM</em> variant which might induce potential cardiovascular toxicity of anticancer Niraparib therapies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 25-30"},"PeriodicalIF":1.4,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of HER2, KRAS, and PIK3CA mutations in uterine cervical neuroendocrine carcinoma and implications for oncogenic driver targeting therapy","authors":"Wan-Ru Chao ,&nbsp;Ming-Yung Lee ,&nbsp;Yi-Ju Lee ,&nbsp;Gwo-Tarng Sheu ,&nbsp;Hsiu-Hsiu Chiu ,&nbsp;Huang-Pin Shen ,&nbsp;Chih-Ping Han","doi":"10.1016/j.cancergen.2025.05.005","DOIUrl":"10.1016/j.cancergen.2025.05.005","url":null,"abstract":"<div><h3>Purpose</h3><div>Dysregulated HER2-mediated RAS/MAPK and PI3K/AKT signaling drive uncontrolled cell growth and tumorigenesis. Following our prior report of frequent HER2 mutations in advanced uterine cervical neuroendocrine carcinoma (NEC), this study expands the genomic landscape by investigating KRAS and PIK3CA as potential therapeutic targets in a cohort of 12 Taiwanese women with cervical NEC.</div></div><div><h3>Methods</h3><div>We analyzed 12 histologically confirmed cervical NEC tumor samples from Taiwanese patients. Targeted next-generation sequencing (NGS) was performed using a custom Qiagen GeneRead DNAseq Targeted Panels V2, a clinically relevant tumor panel to detect mutations in key oncogenes. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissues, followed by variant analysis to identify pathogenic alterations.</div></div><div><h3>Results</h3><div>Beyond <em>HER2</em> mutations (41.67 %, 5/12), we detected pathogenic alterations in <em>KRAS</em> (16.67 %, 2/12) and <em>PIK3CA</em> (16.67 %, 2/12) within the same cohort. Concurrent mutations were observed in <em>HER2</em>/<em>KRA</em>S (8.3 %, 1/12) and <em>HER2</em>/<em>PIK3CA</em> (8.3 %, 1/12), indicating potential cooperative effects.</div></div><div><h3>Conclusion</h3><div>This study identifies HER2, KRAS, and PIK3CA as potentially critical drivers in cervical NEC, with their co-occurrence highlighting the role of RAS/MAPK and PI3K/AKT pathways in pathogenesis. Dual pathway inhibition with multi-target therapies may enhance efficacy and address resistance in this aggressive, treatment-limited disease. Molecular profiling is essential for precision oncology, paving the way for validating these findings in larger cohorts and developing multi-pathway strategies to improve survival and quality of life.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 9-14"},"PeriodicalIF":1.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144177700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}