Cancer Genetics最新文献

SATB2 plays a critical role in pancreatic cancer cell proliferation, migration and T cell cytotoxicity SATB2在胰腺癌细胞增殖、迁移和T细胞毒性中起关键作用

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-06-17 DOI: 10.1016/j.cancergen.2025.06.006

Guixing Jiang , Xinyang Zhou , Shehuang Chen , Faming Zhong , Gaoshi Huang , Bicheng Wu , Qiaoyan Mou , Gang Jiang , Tianyu Lin

{"title":"SATB2 plays a critical role in pancreatic cancer cell proliferation, migration and T cell cytotoxicity","authors":"Guixing Jiang , Xinyang Zhou , Shehuang Chen , Faming Zhong , Gaoshi Huang , Bicheng Wu , Qiaoyan Mou , Gang Jiang , 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}

引用次数: 0

METTL3-mediated m6A modification of pri-miR-93 promotes hepatocellular carcinoma progression via CDKN1A suppression mettl3介导的m6A修饰pri-miR-93通过抑制CDKN1A促进肝细胞癌的进展

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-06-11 DOI: 10.1016/j.cancergen.2025.06.003

Yue Wang , Xiaorong Zhang , Fan Yang, Jiaqi Shang, Qing Yang

{"title":"METTL3-mediated m6A modification of pri-miR-93 promotes hepatocellular carcinoma progression via CDKN1A suppression","authors":"Yue Wang , Xiaorong Zhang , Fan Yang, Jiaqi Shang, 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 (m<sup>6</sup>A) 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 m<sup>6</sup>A modification in HCC may provide valuable insights into its molecular mechanisms.</div><div>This study found that METTL3, an m<sup>6</sup>A 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 m<sup>6</sup>A-dependent manner, miR-93–5p was selected for further study. Experimental results demonstrated that METTL3-mediated m<sup>6</sup>A 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 m<sup>6</sup>A 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 m<sup>6</sup>A 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}

引用次数: 0

Comprehensive molecular profiling in MOTION study 运动研究中的综合分子分析

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-06-10 DOI: 10.1016/j.cancergen.2025.06.001

Olesya A. Kuznetsova , Maxim V. Ivanov , Alexandra A. Lebedeva , Alexey A. Tryakin , Egor M Veselovsky , Maria S. Cheporova , Fedor V. Moiseenko , Margarita S. Gileva , Alena I. Cherentsova , Anna N. Tiatiushkina , Mikhail Y. Fedyanin

{"title":"Comprehensive molecular profiling in MOTION study","authors":"Olesya A. Kuznetsova , Maxim V. Ivanov , Alexandra A. Lebedeva , Alexey A. Tryakin , Egor M Veselovsky , Maria S. Cheporova , Fedor V. Moiseenko , Margarita S. Gileva , Alena I. Cherentsova , Anna N. Tiatiushkina , 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> < 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> < 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}

引用次数: 0

Efficacy of pembrolizumab in MSI-high and BRCA-positive castration-resistant prostate cancer 派姆单抗在msi高和brca阳性去势抵抗性前列腺癌中的疗效

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-06-10 DOI: 10.1016/j.cancergen.2025.06.002

Keita Higa , Satoshi Yamamoto , Koichiro Kurokawa , Koki Watanabe , Hiroki Bamba , Sanji Kanaoka , Kazuyoshi Nakamura

{"title":"Efficacy of pembrolizumab in MSI-high and BRCA-positive castration-resistant prostate cancer","authors":"Keita Higa , Satoshi Yamamoto , Koichiro Kurokawa , Koki Watanabe , Hiroki Bamba , Sanji Kanaoka , 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}

引用次数: 0

The Interplay of N6-Methyladenosine and Ferroptosis in Cancer: A Promising Therapeutic Avenue n6 -甲基腺苷和铁下垂在癌症中的相互作用：一个有前途的治疗途径

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-06-01 DOI: 10.1016/j.cancergen.2025.05.007

Kirthik Roshan M , Rituparna Pal , Subhadra Kumari, Santosh Kumar, Srinivasan Muthuswamy

{"title":"The Interplay of N6-Methyladenosine and Ferroptosis in Cancer: A Promising Therapeutic Avenue","authors":"Kirthik Roshan M , Rituparna Pal , Subhadra Kumari, Santosh Kumar, 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}

引用次数: 0

Acute cardiac dysfunction in patients with ovarian cancer treated with Niraparib due to TFAM mutation: A case series and functional analysis 因TFAM突变而接受尼拉帕尼治疗的卵巢癌患者的急性心功能障碍：病例系列和功能分析

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-05-25 DOI: 10.1016/j.cancergen.2025.05.006

Fei Liu , Wen Liu , Danya Li , Chunhua Tu , Xiaoping Peng , Yuan Wen

{"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 , Wen Liu , Danya Li , Chunhua Tu , Xiaoping Peng , 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>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>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}

引用次数: 0

Profiling of HER2, KRAS, and PIK3CA mutations in uterine cervical neuroendocrine carcinoma and implications for oncogenic driver targeting therapy HER2、KRAS和PIK3CA在子宫颈神经内分泌癌中的突变及其对肿瘤驱动靶向治疗的意义

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-05-24 DOI: 10.1016/j.cancergen.2025.05.005

Wan-Ru Chao , Ming-Yung Lee , Yi-Ju Lee , Gwo-Tarng Sheu , Hsiu-Hsiu Chiu , Huang-Pin Shen , Chih-Ping Han

{"title":"Profiling of HER2, KRAS, and PIK3CA mutations in uterine cervical neuroendocrine carcinoma and implications for oncogenic driver targeting therapy","authors":"Wan-Ru Chao , Ming-Yung Lee , Yi-Ju Lee , Gwo-Tarng Sheu , Hsiu-Hsiu Chiu , Huang-Pin Shen , 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}

引用次数: 0

Corrigendum to “Omics approaches: Role in acute myeloid leukemia biomarker discovery and therapy” [Cancer Genetics, 2025, Volume: 292-293, Pages: 14-26/https://doi.org/10.1016/j.cancergen.2024.12.006] “组学方法：在急性髓性白血病生物标志物发现和治疗中的作用”的勘误表[癌症遗传学，2025，卷：292-293，页：14-26/https://doi.org/10.1016/j.cancergen.2024.12.006]

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-05-20 DOI: 10.1016/j.cancergen.2025.05.002

Fatemeh Sadat Shafiei , Saeid Abroun , Sadaf Vahdat , Mohammad Rafiee

引用次数: 0

HRD status variation in consecutive tumour biopsies in a pan-cancer cohort: a descriptive single-center study including patients from the Phase 1 Unit, Copenhagen University Hospital, Rigshospitalet 在一项泛癌症队列中，连续肿瘤活检的HRD状态变化：一项描述性单中心研究，包括来自Rigshospitalet哥本哈根大学医院i期病房的患者

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-05-20 DOI: 10.1016/j.cancergen.2025.05.004

Rosa Damkjær Britton , Daniela Alosi , Luca Robinson , Ida Kappel Buhl , Iben Spanggaard , Martin Højgaard , Maj Kamille Kjeldsen , Maria Rossing , Ulrik Lassen , Kristoffer Staal Rohrberg

{"title":"HRD status variation in consecutive tumour biopsies in a pan-cancer cohort: a descriptive single-center study including patients from the Phase 1 Unit, Copenhagen University Hospital, Rigshospitalet","authors":"Rosa Damkjær Britton , Daniela Alosi , Luca Robinson , Ida Kappel Buhl , Iben Spanggaard , Martin Højgaard , Maj Kamille Kjeldsen , Maria Rossing , Ulrik Lassen , Kristoffer Staal Rohrberg","doi":"10.1016/j.cancergen.2025.05.004","DOIUrl":"10.1016/j.cancergen.2025.05.004","url":null,"abstract":"<div><h3>Background</h3><div>Limited data on the evolution of homologous recombination deficiency (HRD) status within the course of disease increases the risk of inaccuracies in deciding on Poly(ADP-ribose) polymerase inhibitor therapy and questions the necessity for confirmatory biopsies in clinical trials. This study aims to assess HRD status over time and its role as a dynamic biomarker.</div></div><div><h3>Methods</h3><div>Genomic tumour profiles obtained from cancer patients in a Phase 1 Unit were retrospectively analysed. Patients with >1 tumour tissue sample and available genomic tumour profiles were included. HRD scores were assessed according to the method described by Telli et al. (2016).</div></div><div><h3>Results</h3><div>A total of 108 patients were included across 24 cancer diagnoses. A potential therapy-altering shift in HRD status was observed in 17 patients: 12 went from negative to positive HRD status whilst 5 went from positive to negative.</div></div><div><h3>Discussion</h3><div>When testing for HRD, sensitivity to normal tissue in tumour samples has proven more consequential than previously expected. Based on our findings, HRD status rarely changes over time, and changes in HRD scores may not reflect a genuine biological shift. Therefore, patients considered for clinical trials based on historic HRD status may not need confirmatory biopsies after intervening treatment, thereby sparing patients from unnecessary procedures.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 1-8"},"PeriodicalIF":1.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144138605","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}

引用次数: 0

Potential factors underlying the progression of RUNX1-mutated MDS to AML runx1突变MDS发展为AML的潜在因素

IF 1.4 4区医学

Cancer Genetics Pub Date : 2025-05-15 DOI: 10.1016/j.cancergen.2025.05.003

Anna Stengel, Katharina Hörst, Constanze Kühn, Manja Meggendorfer, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach

{"title":"Potential factors underlying the progression of RUNX1-mutated MDS to AML","authors":"Anna Stengel, Katharina Hörst, Constanze Kühn, Manja Meggendorfer, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach","doi":"10.1016/j.cancergen.2025.05.003","DOIUrl":"10.1016/j.cancergen.2025.05.003","url":null,"abstract":"<div><div>This study explores the molecular distinctions between myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) with <em>RUNX1</em> mutations (<em>RUNX1</em>mut), aiming to elucidate factors influencing the progression from MDS to AML. Analyzing 1520 patients (773 AML and 747 MDS cases), <em>RUNX1</em>mut were present in 10 % of MDS and 13 % of AML cases. Interestingly, <em>RUNX1</em>mut were associated with higher blast counts in MDS, suggesting a potential role in disease progression. Despite similar overall survival across subgroups, significant differences in variant allele frequency (VAF) were observed, correlating with blast count. Our study highlights a unique genetic signature in both <em>RUNX1</em>mut MDS and AML: Cytogenetic analysis showed a higher frequency of normal karyotypes in <em>RUNX1</em>mut-MDS compared to <em>RUNX1</em>mut-AML. While only trisomy 8 was found in MDS, trisomies 8, 11, and 13 were detected in <em>RUNX1</em>mut-AML. Notably, <em>MECOM</em> rearrangements, <em>KMT2A</em>-PTD, and <em>FLT3</em>-ITD alterations were exclusive to RUNX1mut-AML. <em>RUNX1</em> mutations were strongly associated with spliceosome gene mutations, especially in <em>RUNX1</em>mut-MDS. Copy neutral loss of heterozygosity (CN-LOH) involving <em>RUNX1</em> was detected in 22 % of <em>RUNX1</em>mut-AML cases but was absent in <em>RUNX1</em>mut-MDS. These findings highlight the distinct genetic landscape of <em>RUNX1</em>mut-MDS and AML. Understanding these molecular determinants may enhance monitoring and early intervention strategies for MDS patients at risk of progression to AML.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"294 ","pages":"Pages 181-183"},"PeriodicalIF":1.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090362","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}

引用次数: 0