Cancer Genetics最新文献

{"title":"Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach","authors":"Junkyu Kim ,&nbsp;Hye-Lim Jang ,&nbsp;Jung Young Hong ,&nbsp;Seung Tae Kim ,&nbsp;Se Hoon Park ,&nbsp;Joon Oh Park ,&nbsp;Kyoung-Mee Kim ,&nbsp;Deok geun Kim ,&nbsp;Jeeyun Lee ,&nbsp;Sung Hee Lim","doi":"10.1016/j.cancergen.2025.07.006","DOIUrl":"10.1016/j.cancergen.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the <em>PIK3CA</em> gene. Recent advancements have shown effective treatment for patients with <em>PIK3CA</em>-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.</div></div><div><h3>Methods</h3><div>From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3886 patients with 36 different cancer types at the Samsung Medical Center. The incidence of <em>PIK3CA</em> mutations and amplifications according to cancer type and their correlation with the tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) status were reviewed. Mutation sites were also identified.</div></div><div><h3>Results</h3><div>Among the 3886 patients, <em>PIK3CA</em> mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring <em>PIK3CA</em> mutations demonstrated significantly higher TMB and MSI-high rates than those without (31.8 % vs. 12.5 % for TMB and 7.8 % vs. 1.6 % for MSI-high, respectively, <em>p</em> = 0.001). In contrast, <em>PIK3CA</em> amplifications were observed in 1.3 % (51/3886) of patients, primarily in gastric, bladder, and colorectal cancers, and associated with lower TMB, MSI-high, and HRD rates. PIK3CA fusions were identified in three patients. The most common mutation sites were E545K, E542K, and H1047R.</div></div><div><h3>Conclusion</h3><div>Of 3886 patients with metastatic solid tumors, 358(9.2 %) had <em>PIK3CA</em> mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 133-143"},"PeriodicalIF":1.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656551","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":"Upregulation of Uracil DNA Glycosylase (UNG) in Prostate Cancer","authors":"Vahid Rouhi ,&nbsp;Sanaz Habibi ,&nbsp;Dr. Hikmet Koseoglu ,&nbsp;Dr. Emre Ari ,&nbsp;Mehmet Guven","doi":"10.1016/j.cancergen.2025.07.005","DOIUrl":"10.1016/j.cancergen.2025.07.005","url":null,"abstract":"<div><div>Prostate cancer is the second most common malignancy and a major cause of cancerrelated deaths in men. Dysregulation of DNA repair mechanisms, particularly those involved in base excision repair (BER), contributes significantly to carcinogenesis. Alterations in this pathway have been linked to aggressive tumor behavior, early recurrence, and poor survival, positioning DNA repair as a promising therapeutic target. This study focused on the expression of two BER genes, uracil DNA glycosylase (UNG) and 8-oxoguanine DNA glycosylase (OGG1), in tumor and adjacent normal prostate tissues. Fifty prostate cancer patients were enrolled. Tumor and adjacent normal tissues were obtained using tru-cut biopsy. Gene expression levels of UNG and OGG1 were assessed by quantitative real-time PCR. UNG expression was significantly elevated in tumor tissues compared to normal tissues, showing a 3.39-fold increase (<em>p</em> = 0.02). OGG1 expression also increased by 2.60-fold, but this was not statistically significant (<em>p</em> &gt; 0.05). A positive correlation was observed between UNG expression and PSA levels in tumor tissues (<em>r</em> = 0.341, <em>p</em> = 0.01). No statistically significant difference in gene expression was found between tumor and normal tissues with respect to clinical parameters such as diabetes, hypertension, PIRADS score, Gleason score, smoking status, or presence of nodules. UNG is significantly upregulated in prostate cancer and may help maintain genomic stability and tumor cell survival. Targeting UNG alongside DNA-damaging therapies could disrupt cancer progression. Further studies on BER genes may support personalized treatment approaches in prostate cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 130-132"},"PeriodicalIF":1.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611724","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":"Tandem duplication and triplication in BRCA1: revisiting the large genomic rearrangements via optical genome mapping","authors":"B Aldrige Allister ,&nbsp;Jonathan L Lühmann ,&nbsp;Lena Wendeburg ,&nbsp;Frank Dechend ,&nbsp;Carmela Beger ,&nbsp;Stefanie Tölle ,&nbsp;Julia von Ehr ,&nbsp;Tim Ripperger ,&nbsp;Bernd Auber ,&nbsp;Nataliya di Donato ,&nbsp;Doris Steinemann","doi":"10.1016/j.cancergen.2025.07.002","DOIUrl":"10.1016/j.cancergen.2025.07.002","url":null,"abstract":"<div><div>Large genomic rearrangements (LGRs) within the human genome are becoming more recognized by novel genome-wide technologies and may be underreported so far. This class of genomic variation includes copy number variations like duplications or triplications of coding or non-coding genomic regions. Here, we report two LGRs targeting <em>BRCA1</em>, a duplication of exons 18–19 and a triplication of exons 1–2 in two independent families. Utilizing Optical Genome Mapping (OGM), Whole Genome Sequencing (WGS) and cDNA analysis, we characterized the genomic organization and transcriptomic effects of these LGRs regarding its. We show that the tandem duplication ogm[GRCh38]dup(17)(q21.31q21.31)(43057052_43063373), targeting <em>BRCA1</em> exon 18–19 is predicted to generate a premature termination codon, namely p.(His1732Metfs*10). The triplication of <em>BRCA1</em> exon 1–2 ogm[GRCh38]trip(17)(q21.31q21.31)(43117155_43124115) is also sequentially arranged. The transcript shows an insertion of a small part of intron 2 (chr17:43,121,558–43,121,676) that theoretically will generate a premature termination codon as well. Collectively, OGM and WGS help elucidating the architecture of these LGRs. However, the final curation depends on how adequate the functional consequences of these LGR can be clarified. Deeper investigation of LGRs on transcript level is important to attain accurate conclusions with respect to therapeutic decisions.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 125-129"},"PeriodicalIF":1.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614664","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":"TFAP2E acts as a tumor suppressor by regulating cell cycle progression in oral squamous cell carcinoma cells","authors":"Ryo Sakai ,&nbsp;Yoshinori Inagaki ,&nbsp;Haruno Tsurumi ,&nbsp;Akiko Ohashi ,&nbsp;Tadateru Takayama ,&nbsp;Shuichi Sato ,&nbsp;Kyoko Fujiwara","doi":"10.1016/j.cancergen.2025.07.004","DOIUrl":"10.1016/j.cancergen.2025.07.004","url":null,"abstract":"<div><div>TFAP2E, a member of the activator protein-2 transcription factor family, is considered to act as a tumor suppressor. Lower TFAP2E expression is associated with poor prognosis in patients with different cancer types. <em>TFAP2E</em> gene is located on chromosome 1q34, where is commonly deleted region in the cancer genome. Our previous research indicated that TFAP2E suppresses cell growth by regulating cell cycle progression from the G2 to M phase. However, as the analyses were performed using asynchronized cells, other possibilities cannot be ruled out. The present study aimed to analyze the effects of <em>TFAP2E</em> silencing on synchronized cells. Human oral squamous cell carcinoma (OSCC)-derived Ca9–22 cells were stably transfected with TFAP2E-short hairpin RNA and synchronized to the late-G1 phase using double thymidine block. Cell cycle progression rate was analyzed by periodically examining cell cycle distribution patterns using fluorescence-activated cell sorting analysis. TFAP2E-knockdown cells showed a rapid exit from the M-phase compared with control cells; meanwhile, no difference was observed between the cells until the end of S-phase. Additionally, rapid M-phase exit was not observed in TFAP2E-knockdown cells following release from nocodazole-mediated synchronization to the G2/M-phase. These observations indicated that TFAP2E-knockdown results in rapid cell cycle progression from the G2 to M phase. Overall, current findings suggest that TFAP2E acts as a tumor suppressor by regulating cell cycle progression at least in OSCC cells.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 111-116"},"PeriodicalIF":1.4,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596505","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":"Influence of IL-38 as a novel biomarker on the pathophysiological processes of esophageal cancer","authors":"Dehua Zeng ,&nbsp;Shixin Ye ,&nbsp;Wenmin Yin ,&nbsp;Duohuang Lian ,&nbsp;Shunkai Zhou","doi":"10.1016/j.cancergen.2025.06.010","DOIUrl":"10.1016/j.cancergen.2025.06.010","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer.</div></div><div><h3>Methods</h3><div>Differential protein expression between esophageal tumor tissue and adjacent normal tissue was analyzed using proteomics in a mouse model of esophageal cancer. Differential proteins were identified through bioinformatics analysis. The mechanisms of action of differential proteins in esophageal cancer were validated using techniques such as western blotting and immunohistochemistry.</div></div><div><h3>Results</h3><div>Proteomic analysis revealed that IL-38 exhibited the greatest differential expression. Molecular biology techniques including western blotting and immunohistochemistry demonstrated that IL-38 modulates Regulatory T cell (Treg)/ T helper 17 cell (Th17) balance through the Sirtuin 1 (SIRT1)/ hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway in esophageal cancer.</div></div><div><h3>Conclusion</h3><div>IL-38 is a novel biomarker for esophageal cancer and regulates Treg/Th17 balance through the Sirt1/HIF-1α signaling pathway, providing new insights for the treatment of esophageal cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 117-124"},"PeriodicalIF":1.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596506","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":"ADAR1 gene expression and its importance in breast cancer","authors":"Bulent Tekin ,&nbsp;Seda Ekizoglu ,&nbsp;Sare Burcu Kaya ,&nbsp;Mehmet Guven ,&nbsp;Didem Can Trabulus","doi":"10.1016/j.cancergen.2025.06.011","DOIUrl":"10.1016/j.cancergen.2025.06.011","url":null,"abstract":"<div><div>RNA editing mediated by ADAR1 is vital for the survival of mammals, and its malfunction leads to irregular editing of its targets, potentially influencing the observable characteristics of breast cancer. The study aims to investigate ADAR1- p110 and ADAR1-p150 gene expression in breast cancer patients' tissue samples (tumor and normal), to determine the role of this expression in tumor development, and to correlate expression levels with patients' clinical findings to understand breast cancer heterogeneity. In this research, we used tumor and adjacent normal tissue samples from 75 patients diagnosed with breast cancer who had undergone surgery. The levels of gene expression were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study found that ADAR1-p110 expression was significantly higher (1.32-fold, <em>p</em> &lt; 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, <em>p</em> &lt; 0.0001) in tumor tissue compared to normal tissue. ADAR1-p150 expression was significantly higher in ER (estrogen receptors )-positive patients compared to ER-negative patients (<em>p</em> = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (<em>p</em> = 0.02). Our findings, obtained by using tumor and normal tissue from the same individual, demonstrate increased ADAR1 gene expression in tumor tissue. Considering the literature data indicating ADAR1′s association with drug resistance and the correlation we observed between ADAR1 expression levels and certain clinicopathological data of the patients, it is evident that ADAR1 expression is a parameter that should be taken into account in treatment planning.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 106-110"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571030","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":"Two MLN-TK patients with ETV::ABL1 fusions mediated by different mechanisms with false negative FISH results resolved with RNA fusion analysis","authors":"Patrick Maher ,&nbsp;Tim Jang ,&nbsp;Ruben Ruiz Vega ,&nbsp;Jennifer Miatech ,&nbsp;Gabriela Bastidas Mora ,&nbsp;W.J.R. Quan ,&nbsp;Reeba Prince ,&nbsp;Joanna Chaffin ,&nbsp;Lijun Yang ,&nbsp;Petr Starostik ,&nbsp;Rachel D. Burnside","doi":"10.1016/j.cancergen.2025.06.007","DOIUrl":"10.1016/j.cancergen.2025.06.007","url":null,"abstract":"<div><div>Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusions (MLN-TK) is a newly added entity in the World Health Organization (WHO) 5^th Edition, and within this category, <em>ETV6::ABL1</em> gene fusions are the most commonly reported in the literature. While patients may respond favorably to tyrosine kinase inhibitor (TKI) therapy, prognosis is generally less favorable than for <em>BCR::ABL1</em>-positive chronic myelogenous leukemia (CML), also treated with tyrosine kinase inhibitor therapy (TKIs). We report two patients diagnosed with MLN-TK, both of whom were positive for <em>ETV6::ABL1</em> gene fusions, albeit by different mechanisms but with the same breakpoints. Importantly, one of our subjects also demonstrated <em>BCR::ABL1</em> fusion subclonally to the <em>ETV6::ABL1</em> fusion positive clone. This study emphasizes the importance of resolving false negative and/or discrepant fluorescence in situ hybridization (FISH) results using alternative methods, such as RNA fusion analysis, to aid in the diagnosis of MLN-TK.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 100-105"},"PeriodicalIF":1.4,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564004","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":"GPX4 in triple-negative breast cancer: A key regulator of ferroptosis and therapeutic target","authors":"Gomathy Baskar","doi":"10.1016/j.cancergen.2025.06.009","DOIUrl":"10.1016/j.cancergen.2025.06.009","url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer among women globally. Triple-negative breast cancer (TNBC) is an exceptionally aggressive and challenging kind of breast cancer to manage. Triple-negative breast cancer (TNBC) lacks oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). As a result, there are no effective targeted therapies for it, and it doesn't respond well to standard treatment. Platinum-based treatments and neoadjuvant chemotherapy have shown promise, but the outlook is still not good. Ferroptosis, a type of regulated cell death that depends on iron, is a new way to treat diseases. Ferroptosis inducers like erastin may help make TNBC cells more sensitive to treatment, but they are still hard to deliver because they are toxic and don't dissolve well. Nanotechnology and drug delivery systems, especially exosome-based carriers, are promising ways to get around these problems. Exosomes are a new way to deliver drugs that cause ferroptosis because they are biocompatible and can target specific cells. This is a very interesting area for developing new treatments for TNBC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 76-83"},"PeriodicalIF":1.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523587","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":"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}