Cancer Genetics最新文献_第2页

Tumor-normal sequencing reveals novel TP53 germline and clinically actionable somatic mutations in Nigerian breast cancer patients 肿瘤正常测序揭示了尼日利亚乳腺癌患者中新的TP53种系和临床可操作的体细胞突变。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-26 DOI: 10.1016/j.cancergen.2025.11.012

Abimbola F. Onyia , AbdulRazzaq Lawal , Chidiebere Ogo , Ebenezer S. Nkom , Nwamaka N. Lasebikan , Olaitan T. Ayegbusi , Opeyemi C. De Campos , Oluwakemi A. Rotimi , Jelili O. Oyelade , Usman M. Aliyu , Emeka E.J. Iweala , Solomon O. Rotimi

Purpose

Disparities in the care and management of breast cancer (BC) contribute to poor outcomes and limited access to precision oncology in Nigerian patients. Existing studies on Nigerian patients have largely been conducted abroad, restricting their direct application to local healthcare. This study addresses this gap through a locally led investigation of germline and somatic mutations using tumor-normal paired sequencing.

Methods

Forty-two female BC patients were recruited from teaching hospitals between January and April 2024. DNA was extracted from blood and matched fresh-frozen tumor tissue. Targeted sequencing of 50 cancer-related genes was performed with the Illumina AmpliSeq Cancer Hotspot Panel and MiSeq platform. Germline and somatic variants were identified through matched normal filtering, with oncogenic significance assessed using the ESCAT/ESMO Tier classification. Visualization was performed in R (v4.4.2) using the maftools package.

Results

A germline TP53 pathogenic variant, TP53 c.694dupA (p.Ile232Asnfs) was identified in a 35-year-old triple-negative BC patient with recurrent metastatic disease, representing its first report as a germline alteration. Additionally, eighteen oncogenic/likely oncogenic somatic variants were detected, nine of which were actionable (Tier I-III). EGFR amplification was found in 7 % of patients, alongside copy number losses in genes including CDKN2A and KIT.

Conclusion

This study demonstrates the feasibility of localized tumor-normal sequencing in Nigerian BC patients, revealing actionable variants with clinical relevance. These findings highlight the need to integrate genomic profiling into routine cancer care and establish molecular tumor boards to advance precision oncology in Nigeria.

目的：尼日利亚乳腺癌（BC）护理和管理的差异导致预后不佳，并限制了患者获得精确肿瘤治疗的机会。对尼日利亚患者的现有研究主要是在国外进行的，限制了其直接应用于当地医疗保健。本研究通过使用肿瘤-正常配对测序对生殖系和体细胞突变进行局部主导的研究，解决了这一差距。方法：于2024年1月至4月在教学医院招募42例女性BC患者。从血液和匹配的新鲜冷冻肿瘤组织中提取DNA。利用Illumina AmpliSeq Cancer Hotspot Panel和MiSeq平台对50个癌症相关基因进行靶向测序。通过匹配的正常过滤鉴定种系和体细胞变异，并使用ESCAT/ESMO分级评估致癌意义。可视化是在R （v4.4.2）中使用maftools包执行的。结果：一种种系TP53致病变异，TP53 c.694dupA （p.i ile232asnfs）在一名35岁的三阴性BC患者复发性转移性疾病中被发现，这是其作为种系改变的首次报道。此外，检测到18个致癌/可能致癌的体细胞变异，其中9个是可操作的（I-III级）。在7%的患者中发现EGFR扩增，同时CDKN2A和KIT等基因的拷贝数丢失。结论：本研究证明了尼日利亚BC患者局部肿瘤-正常测序的可行性，揭示了具有临床相关性的可操作变异。这些发现突出了将基因组图谱纳入常规癌症治疗和建立分子肿瘤委员会以在尼日利亚推进精准肿瘤学的必要性。

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引用次数: 0

Quantitative and qualitative methods for measuring chromosomal instability in tumor cells 测定肿瘤细胞染色体不稳定性的定量和定性方法。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-24 DOI: 10.1016/j.cancergen.2025.11.008

Hanna Karolina de Araújo Batistão , João Marcos Oliveira-Silva , Vinícius Bernardo Oliveira , Isaac Iogan de Araújo Batistão , Angel Mauricio Castro-Gamero

To preserve cellular and tissue homeostasis, cells must maintain a coordinated network of molecular mechanisms that ensure accurate chromosome segregation during mitosis. Errors in this process, such as chromosome mis-segregation, lagging chromosomes in anaphase, centrosome amplification, or chromosome breaks generating non-homologous fusions and dicentric chromosomes, can lead to chromosomal instability (CIN). Persistent CIN promotes chromosomal abnormalities, driving tumor cell proliferation, intratumoral genomic diversity, and ultimately tumor initiation and progression. Tumors exhibiting CIN, characterized by aneuploidy or large-scale structural rearrangements, are strongly associated with metastasis, angiogenesis, and chemoresistance. Despite its biological and clinical relevance, methods to detect, quantify, and evaluate CIN remain poorly standardized. In this work, we critically reviewed the scientific literature to compile and discuss the principal quantitative and qualitative strategies currently available for measuring CIN in vitro.

为了保持细胞和组织的稳态，细胞必须维持一个协调的分子机制网络，以确保有丝分裂过程中染色体的准确分离。这一过程中的错误，如染色体错误分离、后期染色体滞后、中心体扩增或染色体断裂产生非同源融合和双中心染色体，可导致染色体不稳定（CIN）。持续的CIN促进染色体异常，驱动肿瘤细胞增殖，肿瘤内基因组多样性，最终导致肿瘤的发生和发展。表现CIN的肿瘤以非整倍体或大规模结构重排为特征，与转移、血管生成和化疗耐药密切相关。尽管其生物学和临床相关性，检测、量化和评估CIN的方法仍然缺乏标准化。在这项工作中，我们批判性地回顾了科学文献，以汇编和讨论目前可用于体外测量CIN的主要定量和定性策略。

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引用次数: 0

Germline lung cancer SNPs dysregulate known (LATS1) and novel (ADCY2) oncogenes through distal, spatially-constrained eQTLs 生殖系肺癌SNPs通过远端、空间受限的eqtl失调已知（LATS1）和新（ADCY2）癌基因

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-12 DOI: 10.1016/j.cancergen.2025.11.004

Aldric Khoo , Michael Pudjihartono , Justin M. O’Sullivan , William Schierding

Understanding how genomic variants contribute to lung cancer (LC) risk is key to better understanding the molecular mechanisms underlying that risk. While genome-wide association studies (GWAS) have identified numerous LC risk loci, most single nucleotide polymorphisms (SNPs) reside in non-coding regions, making the interpretation of their function challenging. We accounted for lung-specific chromatin interactions and allele-specific gene expression levels in lung tissue to identify novel interactions between LC GWAS SNPs and distal genes. Pathway enrichment analysis implicated eight target genes (CYP2A6, ADCY2, CHRNA3, CHRNA5, LATS1, RAD52, RIF1, TP53BP1) in functional networks involving caffeine metabolism, DNA ionizing radiation (IR)-double strand breaks and cellular response, and nicotine effect on dopaminergic neurons. Novel findings include a role for rs2853677 in ADCY2 dysregulation (previous attribution to TERT) and rs9322193 in targeting tumour suppressor gene LATS1 (previous attribution to RPS18P9/KATNA1). By linking germline variants to more biologically relevant gene targets and somatic processes, our results align more closely with established epidemiological and environmental risk factors for lung cancer, including a potential genetic explanation for the environmental interaction of caffeine and smoking in LC risk. This highlights the value of integrating 3D genome architecture and tissue-specific expression to refine our understanding of cancer susceptibility.

了解基因组变异如何导致肺癌（LC）风险是更好地理解该风险背后的分子机制的关键。虽然全基因组关联研究（GWAS）已经确定了许多LC风险位点，但大多数单核苷酸多态性（snp）位于非编码区，这使得对其功能的解释具有挑战性。我们考虑了肺特异性染色质相互作用和肺组织中等位基因特异性基因表达水平，以确定LC GWAS snp与远端基因之间的新相互作用。途径富集分析发现，8个靶基因（CYP2A6、ADCY2、CHRNA3、CHRNA5、LATS1、RAD52、RIF1、TP53BP1）参与咖啡因代谢、DNA电离辐射（IR）双链断裂和细胞反应以及尼古丁对多巴胺能神经元的影响等功能网络。新的发现包括rs2853677在ADCY2失调（先前归因于TERT）和rs9322193靶向肿瘤抑制基因LATS1（先前归因于RPS18P9/KATNA1）中的作用。通过将种系变异与更多生物学相关的基因靶点和体细胞过程联系起来，我们的研究结果与肺癌的既定流行病学和环境风险因素更紧密地联系在一起，包括咖啡因和吸烟在肺癌风险中的环境相互作用的潜在遗传解释。这突出了整合三维基因组结构和组织特异性表达的价值，以完善我们对癌症易感性的理解。

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引用次数: 0

LncRNA SNHG29 Suppresses Epithelial Ovarian Cancer Cell Invasion and Migration via miR-20b-3p/GNAI3 Axis Regulation LncRNA SNHG29通过miR-20b-3p/GNAI3轴调控抑制上皮性卵巢癌细胞的侵袭和迁移

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.10.105

Chencheng Dai , Nuo Ye , Luyao Wang , Juan Zhou , Sujuan Xu , Yu Jiang , Jiawen Pu , Lei Zhang , Xuemei Jia , Pengfei Xu

Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer in women. Long noncoding RNAs (lncRNAs) are critically involved in malignant progression by modulating proliferation, apoptosis, invasion, metastasis, and chemotherapy resistance. The long noncoding RNA small nucleolar RNA host gene 29 (SNHG29) is involved in multiple malignancies, although its role in EOC has not been elucidated. In our study, SNHG29 expression was significantly downregulated in EOC tissues and was negatively related to lymphatic invasion in EOC patients according to data from the TCGA database. Kaplan–Meier survival analysis revealed that among patients with early stage EOC, compared with patients with low SNHG29 expression levels, patients with high expression levels had markedly longer progression-free survival (PFS) and overall survival (OS) times. Further studies suggested that SNHG29 knockdown enhanced the invasive and migrative potential of EOC cells, whereas SNHG29 overexpression attenuated the invasive and migrative potential capacity. In animal experiments, SNHG29 knockdown significantly promoted lung metastasis in tail vein injection models. Mechanistically, the downregulation of SNHG29 expression inhibited its competitive endogenous RNA activity, resulting in increased miR-20b-3p availability and subsequent degradation of the downstream target gene GNAI3, as determined by RNA immunoprecipitation (RIP) and luciferase reporter gene assays. miR-20b-3p inhibition significantly reduces the invasive and metastatic capabilities of EOC cells resulting from a reduction in SNHG29 expression. Our study revealed that SNHG29 may be a promising prognostic factor and therapeutic target for EOC.

上皮性卵巢癌（EOC）是女性最致命的妇科癌症。长链非编码rna （lncRNAs）通过调节增殖、凋亡、侵袭、转移和化疗耐药性，在恶性肿瘤的进展中起着至关重要的作用。长链非编码RNA小核仁RNA宿主基因29 （SNHG29）参与多种恶性肿瘤，尽管其在EOC中的作用尚未阐明。在我们的研究中，TCGA数据库的数据显示，SNHG29在EOC组织中表达显著下调，并且与EOC患者淋巴浸润呈负相关。Kaplan-Meier生存分析显示，在早期EOC患者中，与SNHG29低表达水平患者相比，高表达水平患者的无进展生存期（PFS）和总生存期（OS）时间明显延长。进一步的研究表明，SNHG29的敲低增强了EOC细胞的侵袭和迁移潜能，而SNHG29的过表达则减弱了EOC细胞的侵袭和迁移潜能。动物实验中，敲低SNHG29可显著促进尾静脉注射模型的肺转移。机制上，SNHG29表达的下调抑制了其竞争性内源性RNA活性，导致miR-20b-3p可用性增加，随后下游靶基因GNAI3降解，这是通过RNA免疫沉淀（RIP）和荧光素酶报告基因检测确定的。抑制miR-20b-3p显著降低了EOC细胞的侵袭和转移能力，导致SNHG29表达减少。我们的研究表明，SNHG29可能是EOC的一个有希望的预后因素和治疗靶点。

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引用次数: 0

FBXL16 regulates TAMs recruitment by mediating cytokine release in gliomas FBXL16通过介导胶质瘤细胞因子释放调节tam募集。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.11.006

Zhansheng Fang , Jingying Li , Yu Xiong , Pengxiang Luo , Qi Lu , Miaojing Wu , Kai Huang , Longbo Zhang , Xingen Zhu , Lei Wu

Gliomas are characterized by an immunosuppressive tumor microenvironment (TME), which significantly limits the efficacy of current immunotherapies. To address this challenge, we explored the role of FBXL16, a gene with distinct expression patterns in nervous system tumors identified through analysis of public databases. Our study utilized clinical sample analysis, survival correlation, in vitro functional assays, and in vivo mouse models to investigate FBXL16′s impact on glioma progression. Gene set enrichment analysis (GSEA), immunosuppression profiling, and co-culture assays with flow cytometry validation were employed to elucidate its immunological role, particularly in regulating M2-type tumor-associated macrophage (M2-TAM) recruitment. Our investigation revealed a substantial decrease in FBXL16 expression within glioma tissues, which exhibited and positively correlation with patient survival rates. Overexpression of FBXL16 in glioma cells suppressed proliferation, migration, and invasion, and extended survival in glioma-bearing mice. Mechanistically, FBXL16 regulated the secretion of key immunoregulatory cytokines such as TGF-β, IL-6, IFN-α, and VEGF, thereby disrupting macrophage recruitment to the TME. These findings suggest that FBXL16 attenuates glioma progression by inhibiting cytokine release and limiting TAM recruitment, thus interrupting the immunosuppressive feedback loop within the TME. Our study highlights FBXL16 as a promising immunomodulatory target for glioma therapy, offering new insights into overcoming immunosuppression in gliomas.

胶质瘤的特点是免疫抑制肿瘤微环境（TME），这极大地限制了当前免疫疗法的疗效。为了应对这一挑战，我们探索了FBXL16的作用，FBXL16是一个通过公共数据库分析发现的在神经系统肿瘤中具有不同表达模式的基因。我们的研究利用临床样本分析、生存相关性、体外功能测定和体内小鼠模型来研究FBXL16对胶质瘤进展的影响。采用基因集富集分析（GSEA）、免疫抑制谱和流式细胞术验证的共培养分析来阐明其免疫学作用，特别是在调节m2型肿瘤相关巨噬细胞（M2-TAM）募集方面。我们的研究发现，FBXL16在胶质瘤组织中的表达显著降低，并与患者存活率呈正相关。在胶质瘤细胞中过表达FBXL16可抑制胶质瘤小鼠的增殖、迁移和侵袭，延长存活时间。机制上，FBXL16调节TGF-β、IL-6、IFN-α、VEGF等关键免疫调节细胞因子的分泌，从而破坏巨噬细胞向TME的募集。这些发现表明，FBXL16通过抑制细胞因子释放和限制TAM募集来减缓胶质瘤的进展，从而中断TME内的免疫抑制反馈回路。我们的研究强调了FBXL16作为胶质瘤治疗的一个有前景的免疫调节靶点，为克服胶质瘤的免疫抑制提供了新的见解。

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引用次数: 0

miR-100 polymorphisms as novel genetic risk markers for pediatric acute lymphoblastic leukemia in North African tunisians miR-100多态性作为北非突尼斯儿童急性淋巴细胞白血病的新型遗传风险标记。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.10.099

Amani Dhiflaoui , Amira Daldoul , Saouassen Chouchene , Wafa Chenbeh , Sarra Boukhris , Wassim Y. Almawi , Hassen Ben Abdennebi

Background

While miR-100 is a tumor suppressor in several malignancies, its role in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. This study investigated the relationship between two miR-100 single-nucleotide polymorphisms (SNPs), rs543412 and rs183430, and ALL susceptibility in North African Tunisian children.

Methods

We conducted a case-control study involving 128 pediatric ALL patients and 157 healthy controls. Genotyping of rs543412 and rs183430 was performed using TaqMan SNP assays. Logistic regression analysis was used to assess associations between genotypes, haplotypes, and ALL risk, with multiple corrections applied.

Results

The rs543412 T allele was more frequent in ALL cases than controls (41 % vs. 32 %, p = 0.046), and increased ALL risk was seen with C/T (OR=2.20, 95 %CI=1.03–4.70) and T/T (OR=2.48, 95 %CI=1.16- 5.28) genotypes. However, this association did not survive multiple testing correction. The rs183430 G allele showed stronger association with ALL (57 % vs. 41 %, p < 0.001), and with G/G homozygosity conferring a markedly elevated risk (OR=2.94, 95 %CI:1.56–5.54). Two-locus haplotype analysis revealed that C∼G (aOR=1.77, 95 %CI=1.09–2.88) and T∼G (aOR=2.59, 95 %CI=1.51–4.44) haplotypes significantly increased ALL risk. However, no significant associations were observed between these polymorphisms and the clinicopathological features.

Conclusions

This exploratory study identifies rs183430 as significantly associated with pediatric ALL susceptibility in North African children. These preliminary results suggest that miR-100 SNPs could serve as potential ALL biomarkers, although validation in independent cohorts is needed before clinical use.

背景：虽然miR-100在几种恶性肿瘤中是肿瘤抑制因子，但其在儿童急性淋巴细胞白血病（ALL）中的作用仍知之甚少。本研究调查了两个miR-100单核苷酸多态性（snp） rs543412和rs183430与北非突尼斯儿童ALL易感性之间的关系。方法：我们进行了一项病例对照研究，包括128名儿科ALL患者和157名健康对照者。采用TaqMan SNP检测rss543412和rs183430基因型。采用Logistic回归分析评估基因型、单倍型和ALL风险之间的关系，并进行多次校正。结果：rs543412 T等位基因在ALL患者中的发生率高于对照组（41%比32%，p = 0.046），且C/T （OR=2.20, 95% CI=1.03 ~ 4.70）和T/T （OR=2.48, 95% CI=1.16 ~ 5.28）基因型的ALL风险增加。然而，这种关联并没有经受住多次测试修正。rs183430g等位基因与ALL的相关性较强（57%对41%，p < 0.001），且与G/G纯合性显著升高（OR=2.94, 95% CI:1.56-5.54）。双位点单倍型分析显示，C ~ G （aOR=1.77, 95% CI=1.09-2.88）和T ~ G （aOR=2.59, 95% CI=1.51-4.44）单倍型显著增加ALL风险。然而，没有观察到这些多态性与临床病理特征之间的显著关联。结论：本探索性研究确定rs183430与北非儿童ALL易感性显著相关。这些初步结果表明，miR-100 snp可以作为潜在的ALL生物标志物，尽管在临床使用之前需要在独立队列中进行验证。

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引用次数: 0

Synergistic dual oncogenic role of CKS2 and ACAT2: Enhanced regulatory coherence and biomarker potential in adrenocortical carcinoma CKS2和ACAT2的协同双重致癌作用：肾上腺皮质癌中增强的调节一致性和生物标志物潜力。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.10.103

Javad Omidi

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy with limited therapeutic options and poor clinical outcomes. To identify molecular biomarkers with diagnostic and prognostic relevance, an integrative ceRNA network analysis was performed using transcriptomic profiles from TCGA-ACC and GTEx adrenal tissues. miR-466, the highest-centrality miRNA in the ceRNA network, was used as the focal regulatory component in this framework. Experimentally validated targets were obtained from miRTarBase and miRDB, refined by TargetScan binding-site specificity and correlation-based filtering, and evaluated for tumor-specific expression. Among these candidates, CKS2 and ACAT2 emerged as consistently and significantly upregulated across therapy subgroups, with expression patterns confirmed across patient-level clinical heterogeneity. Both genes demonstrated markedly elevated expression in ACC relative to normal adrenal tissue and exhibited reinforced transcriptional co-regulation in tumors, suggesting a coordinated regulatory shift. Kaplan–Meier survival analyses indicated that high expression of either gene was associated with reduced overall survival, while a multivariate CoxPH model integrating both markers stratified patients into distinct high- and low-risk groups. Additionally, ROC classification demonstrated strong diagnostic performance for distinguishing tumor from normal tissue (AUC = 0.90 for CKS2, 0.88 for ACAT2, and 0.90 for the combined logistic regression model). Functional annotation revealed that CKS2 regulates cyclin-dependent cell cycle transitions, while ACAT2 participates in lipid and fatty-acid metabolic pathways. Together, these roles support a synergistic oncogenic axis in which proliferative acceleration is metabolically sustained, reinforcing tumor growth. These findings nominate CKS2 and ACAT2 as robust biomarkers and mechanistic drivers with translational relevance in ACC.

肾上腺皮质癌（ACC）是一种罕见且高度侵袭性的内分泌恶性肿瘤，治疗选择有限且临床结果较差。为了确定具有诊断和预后相关性的分子生物标志物，使用TCGA-ACC和GTEx肾上腺组织的转录组学图谱进行了综合ceRNA网络分析。miR-466是ceRNA网络中中心性最高的miRNA，在该框架中被用作重点调控成分。从miRTarBase和miRDB中获得实验验证的靶标，通过TargetScan结合位点特异性和相关性过滤进行细化，并评估肿瘤特异性表达。在这些候选基因中，CKS2和ACAT2在治疗亚组中表现出一致且显著的上调，其表达模式在患者水平的临床异质性中得到证实。与正常肾上腺组织相比，这两个基因在ACC中的表达均显著升高，并在肿瘤中表现出增强的转录共调控，表明两者存在协调的调控转变。Kaplan-Meier生存分析表明，任何一种基因的高表达都与总生存率降低有关，而多变量CoxPH模型整合了这两种标记物，将患者分层为不同的高风险和低风险组。此外，ROC分类在区分肿瘤和正常组织方面表现出很强的诊断性能（CKS2的AUC = 0.90， ACAT2的AUC = 0.88，联合逻辑回归模型的AUC = 0.90）。功能注释显示，CKS2调控周期蛋白依赖的细胞周期转变，而ACAT2参与脂质和脂肪酸代谢途径。总之，这些作用支持一个协同的致癌轴，其中增殖加速是代谢持续的，加强肿瘤生长。这些发现表明CKS2和ACAT2是ACC中具有翻译相关性的强有力的生物标志物和机制驱动因素。

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引用次数: 0

Current state of diagnostic genetic testing in pediatric sarcoma: Survey and review by the Cancer Genomics Consortium Sarcoma Working Group 儿童肉瘤诊断基因检测的现状：癌症基因组学联盟肉瘤工作组的调查和回顾。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.10.106

Kathleen M. Schieffer , Renu Bajaj , Selene C. Koo , Josee Lavoie , Dolores Lopez-Terrada , Xinyan Lu , Minjie Luo , Thuy Phung , Teresa A. Smolarek , Maxine Sutcliffe , Jennelle C. Hodge , Cancer Genomics Consortium Sarcoma Working Group

The genomic landscape of pediatric sarcomas is constantly expanding, and the utilization of integrated cytogenetic and molecular evaluation of these tumors for diagnosis, prognostication, and therapeutic implications continues to evolve. As a result, there are diverse approaches to the clinical practice of genomic testing in pediatric sarcomas. The Cancer Genomics Consortium Sarcoma Working Group conducted a survey to understand the current state of diagnostic genetic testing for pediatric sarcomas and assess the challenges faced in the field. Among 46 respondents across the United States and Canada, most utilized conventional karyotyping (61 %) and/or fluorescence in situ hybridization (87 %). Molecular methodologies, such as chromosomal microarray (30 %), targeted RT-PCR (22 %), gene fusion sequencing panels (35 %), pan-cancer sequencing panels (37 %), exome sequencing (11 %), and genome sequencing (7 %) were less frequently implemented clinically. When asked about challenges in the field of pediatric sarcoma, a scarcity of standard practice testing guidelines was noted most commonly, especially in the setting of limited tissue availability. Systematic evidence reviews and guidelines are needed for pediatric sarcomas with a consideration for multidisciplinary and international collaboration of individuals representing both high- and low-resource settings. As a resource in the interim, three case-based testing workflow scenarios are presented based on working group member experience to illustrate how differing technologies could be applied during evaluation considering diagnostic, prognostic and/or therapeutic needs. Finally, emerging technologies that are being applied to the diagnostic genetic evaluation of pediatric sarcomas are described, which upon implementation, may serve to streamline the work-up and further optimize patient care.

儿童肉瘤的基因组图谱正在不断扩大，对这些肿瘤的诊断、预后和治疗意义的综合细胞遗传学和分子评估的应用也在不断发展。因此，在儿童肉瘤的基因组检测的临床实践中有不同的方法。癌症基因组学联盟肉瘤工作组进行了一项调查，以了解儿童肉瘤诊断基因检测的现状，并评估该领域面临的挑战。在美国和加拿大的46个应答者中，大多数使用常规核型（61%）和/或荧光原位杂交（87%）。分子方法，如染色体微阵列（30%）、靶向RT-PCR（22%）、基因融合测序小组（35%）、泛癌症测序小组（37%）、外显子组测序（11%）和基因组测序（7%）在临床上较少使用。当被问及儿童肉瘤领域的挑战时，最常见的是缺乏标准实践测试指南，特别是在组织可用性有限的情况下。需要对儿童肉瘤进行系统的证据审查和指南，同时考虑多学科和国际合作，代表资源丰富和资源匮乏的环境。作为临时资源，本文根据工作组成员的经验提出了三个基于案例的测试工作流程场景，以说明在考虑诊断、预后和/或治疗需求的评估过程中如何应用不同的技术。最后，描述了正在应用于小儿肉瘤诊断基因评估的新兴技术，这些技术一旦实施，可能有助于简化检查并进一步优化患者护理。

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引用次数: 0

WDR54 enhances NF-κB signaling to promote progression of hepatocellular carcinoma WDR54增强NF-κB信号通路促进肝细胞癌进展

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.11.007

Hengyong Zhai , Yanping Du , Hong He , Xiaozhou Shen , Duanmin Hu

Hepatocellular carcinoma (HCC) is a major health threat worldwide. This study found that WDR54 is overexpressed in liver cancer tissues and is inversely correlated with patient prognosis. Through comprehensive cell biology experiments, we demonstrated that WDR54 plays a pivotal role in promoting the malignant proliferation and metastasis of HCC. Further molecular biology investigations, including transcriptome sequencing, revealed that WDR54 exerts its biological effects by modulating the NF-κB signaling pathway. Specifically, WDR54 interacts with RBBP5 to enhance the transcription of p65, thereby promoting HCC proliferation and metastasis. Additionally, the potential impact of WDR54 on tumor cell metabolism and tumor heterogeneity is explored. The findings of this study deepen our understanding of the molecular pathology of liver cancer and lay a foundation for future clinical applications.

肝细胞癌（HCC）是世界范围内的主要健康威胁。本研究发现WDR54在肝癌组织中过表达，且与患者预后呈负相关。通过全面的细胞生物学实验，我们证明了WDR54在促进HCC的恶性增殖和转移中起着关键作用。进一步的分子生物学研究，包括转录组测序，揭示了WDR54通过调节NF-κB信号通路发挥其生物学作用。具体来说，WDR54与RBBP5相互作用，增强p65的转录，从而促进HCC的增殖和转移。此外，我们还探讨了WDR54对肿瘤细胞代谢和肿瘤异质性的潜在影响。本研究结果加深了我们对肝癌分子病理的认识，为今后的临床应用奠定了基础。

引用次数: 0

YME1L facilitates the development of non-small cell lung cancer by promoting activation of mitochondria-Gαi1-Akt pathway YME1L通过激活线粒体- g - αi1- akt通路促进非小细胞肺癌的发生发展。

IF 2.1 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics

Pub Date : 2025-11-01 DOI: 10.1016/j.cancergen.2025.10.101

MinDan Wu , WenXia Qian , MeiJie Xu, JieRu Zhang, Feng Gao, LiXiu Chen, SongHua Huang

As a key regulatory enzyme in mitochondria, YME1L is crucial for regulation of mitochondrial dynamic balance and metabolic plasticity in tumors. Yet its role in non-small cell lung cancer (NACLC) and underlying mechanism are still unclear. In this study, we found YME1L was highly expressed at both protein and RNA levels in NSCLC tissues, which was consistent with the result of database analysis. The bioinformatics analysis also showed that YME1L expression negatively correlated with survival rate. The significance of YME1L was investigated through gain- and loss-of-function studies in vivo and vitro. As expected, the protease activity was consistent with the expression of YME1L. Knockdown of YME1L significantly inhibited mitochondrial activity, proliferation and migration of NACLC cell lines, and suppressed the growth of xenografted tumors in nude mice. While over-expression of YME1L promoted the development of tumors. Further study revealed that YME1L increased the proportion of S-phase and reduced the number of G0/G1 ratio in NSCLC cells, suggesting the strong proliferation activity. Mechanically, knockdown of YME1L decreased the expression of Gαi1 and the phosphorylation of Akt, and on the contrary, YME1L over-expression increased the Gαi1 expression and Akt activation, which in turn stimulated cell proliferation, migration and survival, and promoted the progression of NSCLC. In this study, we revealed that YME1L played a novel oncogenic role in promoting NSCLC tumorigenesis and progression via the mitochondria-Gαi1-AKT axis, providing a new target for the treatment of lung cancer.

作为线粒体的关键调控酶，YME1L在肿瘤组织中对线粒体动态平衡和代谢可塑性的调控起着至关重要的作用。但其在非小细胞肺癌（nclc）中的作用及其机制尚不清楚。本研究中，我们发现YME1L在NSCLC组织中蛋白和RNA水平均高表达，这与数据库分析结果一致。生物信息学分析也显示YME1L表达与存活率呈负相关。通过体内和体外的功能获得和功能丧失研究来研究YME1L的意义。正如预期的那样，蛋白酶活性与YME1L的表达一致。敲低YME1L可显著抑制nclc细胞系线粒体活性、增殖和迁移，抑制裸鼠异种移植肿瘤的生长。而过表达YME1L则促进肿瘤的发展。进一步研究发现，YME1L增加了NSCLC细胞s期比例，降低了G0/G1比，提示其具有较强的增殖活性。机械上，YME1L的下调降低了Gαi1的表达和Akt的磷酸化，相反，YME1L的过表达增加了Gαi1的表达和Akt的激活，从而刺激细胞的增殖、迁移和存活，促进NSCLC的进展。在本研究中，我们发现YME1L通过线粒体- g - αi1- akt轴在促进NSCLC肿瘤发生和进展中发挥了新的致瘤作用，为肺癌的治疗提供了新的靶点。

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