next generation sequencing

下一代测序
  • 文章类型: Journal Article
    通过下一代测序(NGS)进行的可测量残留疾病(MRD)测试结果与接受化疗或来自人类白细胞抗原(HLA)的同种异体移植的成人B细胞急性淋巴细胞白血病(ALL)的复发风险相关。我们研究了93例接受HLA单倍型匹配相关移植的成人B细胞ALL患者在2个疗程的巩固化疗周期后,使用基于NGS的MRD测定靶向免疫球蛋白基因的累积复发率(CIR)和生存预测准确性。使用多参数流式细胞术(MPFC)将预测准确性与MRD测试进行比较。基于NGS的MRD测试在基于MPFC的MRD测试阴性的65名受试者中的28名检测到残留白血病。在Cox回归多变量分析中,基于NGS的MRD测试为阳性的受试者具有较高的3年CIR(危险比[HR]=3.37;95%置信区间[CI],1.34-8.5;P=0.01)和较差的生存率(HR=4.87[1.53-15.53];P=0.007)。一些数据表明,在NGS-MRD测试阳性的移植受者中,CIR较低,生存率较高,但移植的分配不是随机的。我们的数据表明,在预测CIR和生存率方面,NGS的MRD测试比MPFC的测试更准确。(在北京市卫生局注册N2007-1007和中国临床试验注册中心注册[ChiCTR-OCH-10000940和ChiCTROPC-14005546])。
    Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95% Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).
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  • 文章类型: Journal Article
    辣椒是辣椒属(茄科)的成员。它们原产于中美洲和南美洲,由大约35种组成[1,2]。其中,五种(C.annuumL.,C.baccatumL.,C.中国的雅克。,C.frutescensL.,和C.pubescensRuiz&Pav。)已被驯化,主要种植用作蔬菜和香料。在驯化的辣椒中,C.annuum在全球范围内进行商业种植,C.frutescens和C.chinense主要在美国种植,亚洲人,非洲国家[3]。我们比较了农场栽培(FC)和家庭种植(HP)辣椒植物(辣椒)的各个隔室中微生物群的多样性。使用IlluminaNovaSeq6000平台对靶向的16SrRNA基因(V5-V6区)进行测序。变形杆菌,放线菌,酸杆菌,Gemmatimonadota,拟杆菌,FC和HP工厂的所有隔室中都存在Firmicutes。Proteobacteria(或Pseudomonadota)是HP和FC植物所有隔室中的主要门。而放线菌群(或放线菌群)是第二丰富的门。大多数植物隔室(叶子,果实和根)与土壤样品相比,变形杆菌的相对丰度更高。除了少数例外,土壤隔室(散装和根际土壤)显示出较高的门粘菌相对丰度,酸杆菌,Gemmatimonadota,拟杆菌,Nitrosirota,Verrucomicrobiota,和Firmicutes比植物隔间。多样性指数显示,辣椒植物中的细菌群落基于区室和栽培面积而聚集。
    Chillies are members of the genus Capsicum L. (family Solanaceae). They are native to Central and South America and consist of approximately 35 species [1,2]. Among these, five species (C. annuum L., C. baccatum L., C. chinense Jacq., C. frutescens L., and C. pubescens Ruiz & Pav.) have been domesticated and are mainly cultivated for consumption as vegetables and spices. Of the domesticated chillies, C. annuum is commercially cultivated worldwide, while C. frutescens and C. chinense are mainly cultivated in American, Asian, and African countries [3]. We compared the diversity of microbiota in various compartments of farm-cultivated (FC) and home-planted (HP) chilli plants (Capsicum frutescens). Targeted 16S rRNA gene (V5-V6 region) was sequenced using the Illumina NovaSeq 6000 platform. Proteobacteria, Actinobacteriota, Acidobacteriota, Gemmatimonadota, Bacteroidota, and Firmicutes were present in all compartments of both the FC and HP plants. Proteobacteria (or Pseudomonadota) was the predominant phylum in all the compartments of both HP and FC plants, while Actinobacteriota (or Actinomycetota) was the second most abundant phylum. Most plant compartments (leaves, fruits and roots) exhibited a higher relative abundance of Proteobacteria compared to the soil samples. With few exceptions, the soil compartments (bulk and rhizospheric soils) displayed a higher relative abundance of the phyla Myxococcota, Acidobacteriota, Gemmatimonadota, Bacteroidota, Nitrospirota, Verrucomicrobiota, and Firmicutes than the plant compartments. Diversity indices revealed that the bacterial community in chili plants clustered based on both compartment and cultivation area.
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  • 文章类型: Journal Article
    这里,我们呈现,第一次,IonTorrent®下一代测序(NGS)数据为五种鲨鱼(Chondrichthyes:Triakidae),其中包括Galeohinusgaleus(碱基对数(bp)17,487;GenBank登录号ON652874),Mustelusasterias(16,708;ON652873),Mustelusmosis(16,755;ON075077),Musteluspalumbes(16,708;ON075076),和巨翅三重奏(16,746;ON075075)。所有组装的有丝分裂基因组编码13个蛋白质编码基因(PCGs),两个核糖体(r)RNA基因,和22个转移(t)RNA基因(tRNALeu和tRNASer是重复的),除了G.galeus,它包含23个tRNA基因,其中tRNAThr是重复的。本文提供的数据可以帮助其他研究人员进一步阐明triakid物种的多样性以及有丝分裂基因组在公共存储库中积累时Carcharhiniformes(地鲨)内部的系统发育关系。
    Here, we present, for the first time, the Ion TorrentⓇ next-generation sequencing (NGS) data for five houndsharks (Chondrichthyes: Triakidae), which include Galeorhinus galeus (number of bases pairs (bp) 17,487; GenBank accession number ON652874), Mustelus asterias (16,708; ON652873), Mustelus mosis (16,755; ON075077), Mustelus palumbes (16,708; ON075076), and Triakis megalopterus (16,746; ON075075). All assembled mitogenomes encode 13 protein-coding genes (PCGs), two ribosomal (r)RNA genes, and 22 transfer (t)RNA genes (tRNALeu and tRNASer are duplicated), except for G. galeus which contains 23 tRNA genes where tRNAThr is duplicated. The data presented in this paper can assist other researchers in further elucidating the diversification of triakid species and the phylogenetic relationships within Carcharhiniformes (groundsharks) as mitogenomes accumulate in public repositories.
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  • 文章类型: Journal Article
    X连锁微单倍型(X-MHs)有可能成为复杂亲属关系鉴定或DNA混合物分辨率的有价值的补充工具,因为它们汇集了X染色体标记的独特遗传模式和微单倍型(MHs)的益处。在这项研究中,我们使用1000基因组数据库筛选并选择63个X-MHs;通过对112例无关的中国汉族个体的DNA样本进行批量测序评估,筛选出18个MHs.所得的45plex面板在包括重复性在内的综合评估中表现良好,灵敏度,物种特异性,对PCR抑制剂或降解的抗性,突变率,和检测DNA混合物样品的准确性。可以用该组测试的DNA模板的最小量是0.5ng。此外,当男女混合比例大于1:9或男女混合比例大于1:19时,可以准确检测到次要贡献者的等位基因。然后,我们根据从上述112个不相关样本的序列结果获得的等位基因频率数据,计算了每个MH的群体参数.结合每个MH上的这些参数,可以计算出TDPm,TDPf,CPET,CPEDFM,45-plex系统的CPEDFF和CNCEP3分别为1-8.99×10-13、1-1.62×10-19、0.9999999995、0.9999981、0.9955、0.9999971和0.99940,表明该小组有能力进行个人身份和亲子关系测试。为了揭示X-MHs在复杂亲缘关系和男性DNA混合物分析中的独特优势,进行了进一步评估。对于复杂的亲属关系识别,模拟了22种具有不同二级亲属关系的个体对,并分别计算了不同类型的似然比(LR)。结果表明,当将三种类型的二级亲属关系分为三个或四个组时,该小组可以达到大约70%〜80%的准确率。理论上,这样的细分不能通过使用独立的常染色体标记来完成.对于没有嫌疑人的男性DNA混合物分析,我们得出了最大似然比策略,并将其用于男性贡献者数量(NOMC)的估计.进行模拟以验证45-plex面板在该领域的功效,并通过假设45MHs为常染色体标记来将其与常染色体标记进行比较。结果表明,当混合雄性无亲缘关系时,X-MHs在NOMC的估计中比常染色体的估计具有更高的准确性。结果强调了X连锁MHs在复杂亲属关系和男性混合物分析中的独特价值。
    X-linked microhaplotypes (X-MHs) have the potential to be a valuable supplementary tool in complex kinship identification or the resolution of DNA mixtures, because they bring together the distinctive genetic pattern of X chromosomal markers and the benefits of microhaplotypes (MHs). In this study, we used the 1000 Genome database to screen and select 63 X-MHs; 18 MHs were filtered out though a batch sequencing assessment of the DNA samples collected from 112 unrelated Chinese Han individuals. The resulting 45-plex panel performed well in comprehensive assessments including repeatability, sensitivity, species specificity, resistance to PCR inhibitors or degradation, mutation rate, and accuracy in detecting DNA mixture samples. The minimum amount of DNA template that can be tested with this panel is 0.5 ng. Additionally, the alleles of the minor contributor can be accurately detected when the mixture rate is larger than 1:9 in female-male mixture or 1:19 in male-male mixture. Then, we calculated population parameters on each MH based on the allele frequency data obtained from the sequence results of the aforementioned 112 unrelated samples. Combining these parameters on each MH, it can be calculated that TDPm, TDPf, CPET, CPEDFM, CPEDFF and CNCEP3 of the 45-plex system were 1-8.99×10-13, 1-1.62×10-19, 0.9999999995, 0.9999981, 0.9955, 0.9999971 and 0.99940, respectively, indicating that the panel is capable in personal identification and parentage testing. To reveal the unique advantage of X-MHs in the analyses of complex kinship and male DNA mixture, further assessments were made. For complex kinship identification, 22 types of individual pairs with different second-degree kinship were simulated and different types of likelihood ratios (LR) were calculated for each. The results revealed that the panel can achieve accuracy of approximately 70 %∼80 % when dividing each of the three types of second-degree kinships into three or four groups. Theoretically, such sub-division cannot be done by using independent autosomal markers. For male DNA mixture analysis without suspects, the maximum likelihood ratio strategy was derived and employed in the estimation of the number of male contributors (NOMC). Simulations were conducted to verify the efficacy of the 45-plex panel in the field and to compare it with autosomal markers by assuming the 45 MHs as autosomal ones. The results showed that X-MHs can achieve higher accuracy in the estimation of NOMC than autosomal ones when the mixed males were unrelated. The results highlighted the unique value of X-linked MHs in complex kinship and male mixture analyses.
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  • 文章类型: Journal Article
    先天性免疫错误(IEI)的分子诊断在确定患者的长期预后中起着至关重要的作用,治疗方案,和遗传咨询。在过去的十年里,下一代测序(NGS)技术在研究和临床环境中的广泛使用促进了对相当比例的患者进行与IEI相关的基因变异的评估.除了它在诊断已知基因缺陷中的作用,高通量技术的应用,如针对性的,exome,基因组测序导致了新的致病基因的鉴定。然而,从这些不同方法获得的结果可能因疾病表型或患者特征而异.在这项研究中,我们在相当大的IEI患者队列中进行了全外显子组测序(WES),由来自Türkiye21个不同临床免疫学中心的303名个体组成。我们的分析得出了41.1%的患者(297人中有122人)的可能遗传诊断,在6名患者中揭示52种新变异并发现潜在的新IEI基因。理解各种IEI队列结果的重要性不可低估,我们相信我们的发现将对现有文献做出有价值的贡献,并促进临床医生和基础科学研究人员之间的合作研究。
    Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients\' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.
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  • 文章类型: Case Reports
    原发性颅神经淋巴瘤病(PCNL)是原发性CNS淋巴瘤(PCNSL)的一种罕见亚型,其中浸润性淋巴瘤受累仅限于颅神经。这里,我们报告了一例成功进行基因组分析的PCNL病例.一名57岁的男性经历了大约30个月的漫长的诊断前阶段,以由类固醇管理的多次颅神经病发作为特征。在诊断的时候,患者患有右侧颅神经病变,涉及颅神经(CN)V,VI,和七。右侧海绵状病变活检病理结果与大B细胞淋巴瘤浸润神经纤维一致。临床过程是积极的和难治性的,其特征是随着颈脊髓神经淋巴瘤病的发展而不断发展,脑脊液受累,室管膜和脑实质内受累,尽管有多种治疗方法,包括化学免疫疗法,布鲁顿酪氨酸激酶抑制剂,辐射,自体干细胞移植,嵌合抗原受体T细胞疗法(CAR-T),和全脑辐射。患者从最初诊断时和第一次颅神经病变发作后52个月存活了22个月。下一代测序确定的突变(MYD88,CD79b,和PIM1)在PCNSL中经常观察到。不寻常的发现包括涉及PIM1的总共22个突变,表明高度活跃的异常体细胞超突变和两个错义CXCR4突变。CXCR4突变从未在PCNSL中描述过,可能对疾病生物学和治疗干预有影响。我们提供了文献综述以进一步阐明PCNL。
    Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by relentless progression with the development of cervical spinal neurolymphomatosis, cerebrospinal fluid involvement, and ependymal and intraparenchymal cerebral involvement, despite multiple lines of therapy, including chemoimmunotherapy, Bruton\'s tyrosine kinase inhibitor, radiation, autologous stem cell transplant, chimeric antigen receptor T-cell therapy (CAR-T), and whole-brain radiation. The patient survived for 22 months from the time of the initial diagnosis and 52 months after the first episode of cranial neuropathy. Next-generation sequencing identified mutations (MYD88, CD79b, and PIM1) that are frequently observed in PCNSL. The unusual findings included a total of 22 mutations involving PIM1, indicating a highly active aberrant somatic hypermutation and two missense CXCR4 mutations. CXCR4 mutations have never been described in PCNSL and may have implications for disease biology and therapeutic interventions. We provide a literature review to further elucidate PCNL.
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  • 文章类型: Journal Article
    植入前遗传测试(PGT)涉及对通过体外受精(IVF)或卵胞浆内单精子注射(ICSI)产生的早期胚胎进行活检。对活检进行基因检测,以选择移植哪个胚胎。PGT始于1990年代的实验程序,但现在是辅助人类生殖(AHR)的组成部分。PGT允许胚胎选择,这可以降低遗传性疾病传播的风险,并可能减少植入失败和妊娠丢失的机会。这是一个快速发展的领域,这引发了重要的伦理问题。本文旨在简要介绍PGT的历史,概述了PGT的当前证据,并强调了推进这项技术的令人兴奋的研究领域。
    Preimplantation genetic testing (PGT) involves taking a biopsy of an early embryo created through in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Genetic testing is performed on the biopsy, in order to select which embryo to transfer. PGT began as an experimental procedure in the 1990s, but is now an integral part of assisted human reproduction (AHR). PGT allows for embryo selection which can reduce the risk of transmission of inherited disease and may reduce the chance of implantation failure and pregnancy loss. This is a rapidly evolving area, which raises important ethical issues. This review article aims to give a brief history of PGT, an overview of the current evidence in PGT along with highlighting exciting areas of research to advance this technology.
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  • 文章类型: Journal Article
    背景:在全球范围内,SARS-CoV-2病毒在很长一段时间内没有保持其初始基因型,2020年底首次发布全球关注变种(VOCs)报告。随后,基因组测序已成为表征正在进行的大流行的不可或缺的工具,特别是用于从患者或环境监测中获得的SARS-CoV-2样本的分型。对于这种SARS-CoV-2分型,存在各种体外和计算机工作流程,到目前为止,没有系统的跨平台验证报告.
    结果:在这项工作中,我们提出了第一个全面的跨平台评估和验证silicoSARS-CoV-2分型工作流程。评估依赖于在所有相关的现有技术测序平台上用几种不同的体外方法测序的54个患者来源的样品的数据集。此外,我们介绍UnCoVar,一个健壮的,生产级可重复的SARS-CoV-2分型工作流程,在精确度和召回率方面优于所有其他测试方法。
    结论:在许多方面,SARS-CoV-2大流行加速了技术和分析方法的发展。我们认为,这可以作为应对未来流行病的蓝图。因此,UnCoVar很容易推广到其他病毒病原体和未来的大流行。全自动工作流程从患者样本中组装病毒基因组,识别现有的血统,并提供对个体突变的高分辨率见解。UnCoVar包括广泛的质量控制,并自动生成交互式可视化报告。UnCoVar作为Snakemake工作流实现。开源代码可在github.com/IKIM-Essen/uncovar上获得BSD2条款许可。
    BACKGROUND: At a global scale, the SARS-CoV-2 virus did not remain in its initial genotype for a long period of time, with the first global reports of variants of concern (VOCs) in late 2020. Subsequently, genome sequencing has become an indispensable tool for characterizing the ongoing pandemic, particularly for typing SARS-CoV-2 samples obtained from patients or environmental surveillance. For such SARS-CoV-2 typing, various in vitro and in silico workflows exist, yet to date, no systematic cross-platform validation has been reported.
    RESULTS: In this work, we present the first comprehensive cross-platform evaluation and validation of in silico SARS-CoV-2 typing workflows. The evaluation relies on a dataset of 54 patient-derived samples sequenced with several different in vitro approaches on all relevant state-of-the-art sequencing platforms. Moreover, we present UnCoVar, a robust, production-grade reproducible SARS-CoV-2 typing workflow that outperforms all other tested approaches in terms of precision and recall.
    CONCLUSIONS: In many ways, the SARS-CoV-2 pandemic has accelerated the development of techniques and analytical approaches. We believe that this can serve as a blueprint for dealing with future pandemics. Accordingly, UnCoVar is easily generalizable towards other viral pathogens and future pandemics. The fully automated workflow assembles virus genomes from patient samples, identifies existing lineages, and provides high-resolution insights into individual mutations. UnCoVar includes extensive quality control and automatically generates interactive visual reports. UnCoVar is implemented as a Snakemake workflow. The open-source code is available under a BSD 2-clause license at github.com/IKIM-Essen/uncovar.
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  • 文章类型: Journal Article
    HLA-G*01:01:01:34与HLA-G*01:01:01的区别在于内含子3中位置1432处的一个核苷酸(G至A)。
    HLA-G*01:01:01:34 differs from HLA-G*01:01:01:01 by one nucleotide in intron 3 at position 1432 (G to A).
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  • 文章类型: Journal Article
    原发性透明细胞肾细胞癌(ccRCC)的肾切除术后复发的风险仅根据临床标准在日常实践中进行估计。这项研究的目的是评估常见体细胞突变与明确治疗后ccRCC患者的肿瘤侵袭性和预后的相关性。
    使用15基因靶向下一代测序(NGS)小组分析了37例接受根治性肾切除术的ccRCC患者的原发性肿瘤是否存在体细胞突变。在研究队列(n=37)中调查了与组织病理学特征和结果的关联,并在癌症基因组图谱(TCGA)ccRCC队列(n=451)中进行了验证。
    VHL是最常见的突变基因(51%),其次是PBRM1(27%),BAP1(13%),SETD2(13%),KDM5C(5%),ATM(5%),MTOR(5%),和PTEN(3%)。三分之一的患者在15个基因组中没有任何体细胞突变。绝大多数完全没有突变或VHL突变(51%)的肿瘤更常见的是较小的大小(pT1-2)和早期(I/II),而有或没有VHL的各种组合中任何其他基因突变的存在在较大(pT3)和较高分期(III)的肿瘤中富集(p=0.02).在具有未突变的肿瘤或仅VHL突变的患者中没有发现复发,而在具有非VHL体细胞突变的患者中没有发现3次复发(p=0.06)。PBRM1,BAP1,SETD2,KDM5C中存在体细胞突变,ATM,MTOR,451名TCGAccRCC患者中的PTEN基因与肿瘤未改变的患者相比,无病生存期(DFS)显着缩短(q=0.01)。
    这项正在进行的研究的初步发现支持非VHL突变的预后价值,包括PBRM1,BAP1,SETD2,KDM5C,ATM,MTOR,和PTEN在原发性ccRCC肿瘤中作为早期复发的替代和辅助免疫检查点抑制的潜在选择。
    UNASSIGNED: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment.
    UNASSIGNED: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451).
    UNASSIGNED: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non- VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01).
    UNASSIGNED: Preliminary findings from this ongoing study support the prognostic value of non- VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
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