Cancer Genetics[JOURNAL]
Sun
200 papers
High YEATS4 expression characterizes MDM2-amplified liposarcoma.
Mariani A, Sampo M, Sihto H … +2 more , Böhling T, Youssef O
Cancer Genet · 2025 Nov · PMID 40840014 · Publisher ↗
YEATS4 resides within the 12q13-15 chromosomal region, where it is frequently co-amplified with MDM2 and CDK4 in liposarcomas (LPS). However, its independent role in LPS progression and dedifferentiation remains poorly d...
YEATS4 resides within the 12q13-15 chromosomal region, where it is frequently co-amplified with MDM2 and CDK4 in liposarcomas (LPS). However, its independent role in LPS progression and dedifferentiation remains poorly defined. In this study, YEATS4 expression was analyzed in 57 formalin-fixed paraffin-embedded (FFPE) LPS samples using quantitative real-time PCR and compared across histological subtypes. MDM2 amplification status was determined by fluorescence in situ hybridization (FISH). The functional relevance of YEATS4 was assessed via siRNA-mediated knockdown in two well-differentiated LPS (WDLPS) cell lines, GOT-3 and 93T449. Relative YEATS4 mRNA expression was significantly higher in MDM2-positive compared to MDM2-negative tumors (median = 0.413 vs. 0.007; p = 0.008). Using the median YEATS4 expression value (0.227) - calculated from WDLPS and DDLPS cases only - as a threshold, high YEATS4 expression was observed in 64% of high-grade dedifferentiated LPS (DDLPS), 54% of low-grade DDLPS, and 29% of WDLPS cases (p = 0.302). Functionally, YEATS4 silencing significantly reduced cell viability in 93T449 cells at Days 5 (24.1%) and Day 7 (22.1%) compared to control (p < 0.001). In GOT3 cells, a slight reduction was noted at Day 3 (7.6%) which was not sustained. In summary, YEATS4 could contribute to LPS progression in a subset of MDM2-amplified tumors, particularly in high-grade DDLPS. Its variable functional impact across models highlights the complexity of the 12q13-15 amplicon and supports further investigation into YEATS4 as a potential molecular marker and therapeutic target in LPS.
The impact of extracellular vesicles on breast cancer metastasis and therapeutics: genetic considerations.
Jahangiri L
Cancer Genet · 2025 Nov · PMID 40818418 · Publisher ↗
Breast cancer is a significant health problem across the world, and a better understanding of the cellular and molecular properties of the microenvironment in which the breast cancer cells reside is paramount. Breast can...
Breast cancer is a significant health problem across the world, and a better understanding of the cellular and molecular properties of the microenvironment in which the breast cancer cells reside is paramount. Breast cancer cells exhibit an intricate bilateral interaction with the tumour microenvironment, which can contribute to tumour progression. This tumour microenvironment comprises a host of proteins, proteoglycans, glycoproteins, signalling molecules, stromal and immune cells, in addition to extracellular vesicles. Extracellular vesicles encompass a range of vesicles that facilitate cell-to-cell communication and signal relay. Examples of these extracellular vesicles include microvesicles, exosomes and apoptotic bodies. Other categorisations divide extracellular vesicles into exosomes and ectosomes based on their biogenesis. The content of extracellular vesicles can be DNA, RNA, miRNA, proteins, glycans and lipids. This content can affect the tumour microenvironment and tumour metastasis and progression. As such, this review article aims to understand the content of extracellular vesicles and those that promote invasion and metastasis in the context of the tumour microenvironment. The implications of these extracellular vesicles for breast cancer therapeutics will be addressed. Finally, the genes indicated in these processes will be discussed.
Corrigendum to "Resolving HER2 status in breast carcinoma patients with complete deletion of CEP17 in fluorescence in-situ hybridization assays" [Cancer Genetics, 296-297, 2025, 196-199].
Wilcock DM, Zhao J, Gulbahce HE
Cancer Genet · 2025 Sep · PMID 40795754 · Publisher ↗
Abstract loading — click title to view on PubMed.
Genetic silencing of CDC6 via AAV2-Delivered shRNA as a novel cancer genetics-based therapy for cervical carcinoma.
Wang Y, Li X, Lian X … +3 more , Huang B, Jia J, Zhu C
Cancer Genet · 2025 Sep · PMID 40773798 · Publisher ↗
BACKGROUND: Cell division cycle 6 (Cdc6) is an oncogenic driver in cervical cancer, whose dysregulation accelerates S-phase entry and promotes genomic instability. As a key replication licensing factor, its overexpressio...
BACKGROUND: Cell division cycle 6 (Cdc6) is an oncogenic driver in cervical cancer, whose dysregulation accelerates S-phase entry and promotes genomic instability. As a key replication licensing factor, its overexpression creates a cancer-specific vulnerability, making it a promising therapeutic target. OBJECTIVE: To evaluate whether silencing Cdc6 via an adeno-associated virus serotype 2 (AAV2)-delivered shRNA can selectively inhibit cervical cancer growth while sparing normal cells. METHODS: We constructed an AAV2 vector encoding short hairpin RNA (shRNA) targeting Cdc6 and validated its efficacy in vitro using multiple cervical cancer cell lines and an immortalized epithelial cell line (HaCaT). Functional assays assessed cell cycle progression, apoptosis, and DNA damage. Antitumor efficacy was further assessed in xenograft mouse models. RESULTS: AAV2-shCdc6 transduction efficiently silenced Cdc6 expression, leading to G2/M phase arrest, increased γ-H2AX expression, and significant apoptosis in cervical cancer cells. In contrast, normal HaCaT cells exhibited only S-phase arrest without apoptosis. In vivo, AAV2-shCdc6 treatment significantly inhibited tumor growth in xenograft models without observable systemic toxicity. CONCLUSION: AAV2-mediated Cdc6 knockdown selectively targets cervical cancer by exploiting a defined genetic vulnerability. This cancer genetics-based strategy offers a precise and well-tolerated approach for cervical cancer therapy.
Mismatch Repair Cancer Syndrome presenting as synchronous high-grade glioma and diffuse large B cell lymphoma in a pediatric patient.
Massett M, Kendel N, Alali A … +1 more , Wright E
Cancer Genet · 2025 Sep · PMID 40743633 · Publisher ↗
BACKGROUND: Development of multiple distinct, synchronous cancer types in a pediatric patient is very rare and should raise suspicion for an underlying genetic predisposition to cancer. CASE PRESENTATION: We present a pr...
BACKGROUND: Development of multiple distinct, synchronous cancer types in a pediatric patient is very rare and should raise suspicion for an underlying genetic predisposition to cancer. CASE PRESENTATION: We present a previously healthy seven-year-old male who was diagnosed with diffuse large B cell lymphoma after a ruptured appendicitis. During the same hospitalization, he was diagnosed with a high-grade glioma. He underwent subsequent genetic testing, which showed compound heterozygosity for PMS2. He was ultimately diagnosed with Mismatch Repair Cancer Syndrome-4, a subtype of Constitutional Mismatch Repair Deficiency syndrome. His newly discovered cancer predisposition syndrome led to multiple additional family members receiving the same diagnosis, which was especially important in a sibling with leukemia who received hematopoietic stem cell transplantation from an unaffected sibling donor. CONCLUSION: While rare, cancer predisposition syndromes should be suspected in pediatric patients presenting with two or more synchronous, distinct cancer types.
Isolated multinodular goiter and follicular adenoma associated with a novel germline DICER1 variant: A benign presentation.
Chang J, Rabenn R, Parikh A … +1 more , Wu CW
Cancer Genet · 2025 Sep · PMID 40737716 · Publisher ↗
DICER1 syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in DICER1. Pathogenic variants of DICER1 are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovar...
DICER1 syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in DICER1. Pathogenic variants of DICER1 are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovarian sex cord-stromal tumors, and multinodular goiters. We present a family with a novel DICER1 pathogenic variant c.5528-2del who presents with development of isolated thyroid goiters/follicular adenoma. A 44 year old female presents with a past medical history of total thyroidectomy along with her 14-year-old son with a past history of multinodular thyroid goiter confirmed as multifocal follicular adenoma with papillary architecture and her 12-year-old daughter with a past history of multinodular thyroid goiter confirmed as diffuse nodular thyroid hyperplasia. No additional DICER1 syndrome presentations were observed. A genetics panel revealed that the mother, the 14-year-old son, and the 12-year-old daughter share a heterozygous DICER1 c.5528-2del variant, which has not been previously reported. In addition to our direct clinical observations from this family, genetic analysis via in silico prediction models, segregation analysis, and ACMG classification support this variant to be pathogenic. Given the absence of other DICER1 syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. Our findings contribute to the expanding genotype-phenotype correlation in DICER1 syndrome, providing new insights into its variable clinical presentation. Since not all variants are identical, reporting of these observations will advance precision medicine and benefit future patients through more accurate diagnosis, prognosis and personalized management strategies.
Resolving HER2 status in breast carcinoma patients with complete deletion of CEP17 in fluorescence in-situ hybridization assays.
Wilcock DM, Zhao J, Gulbahce HE
Cancer Genet · 2025 Sep · PMID 40737715 · Publisher ↗
OBJECTIVES: To assess the clinicopathologic features of breast cancers with complete CEP17 deletion and determine if alternative testing can resolve their HER2 status. METHODS: Cases with complete CEP17 deletion were ide...
OBJECTIVES: To assess the clinicopathologic features of breast cancers with complete CEP17 deletion and determine if alternative testing can resolve their HER2 status. METHODS: Cases with complete CEP17 deletion were identified, relevant clinicopathologic information was obtained, and fluorescence in-situ hybridization (FISH) was rerun with an alternative chromosome 17 control gene (RAI1, 17p11.2). One case was also evaluated by cytogenomic SNP microarray (CMA). RESULTS: Nine breast carcinoma cases were identified and displayed average HER2 copy numbers ranging from 1.1 to 4.7 (Average: 3.1). HER2 immunohistochemistry (IHC) result was available on 8/9 cases with 2/8 (25 %) displaying no staining, 2/8 (25 %%) displaying 1+ staining and 4/8 (50 %) with 2+ staining. ER and PR IHC were available on 8/9 cases 7/8 (87.5 %) were ER and/or PR positive. RAI1 was present in all cases and, if used in place of CEP17, the ASCO/CAP group classification would have been 2/9 (22.2 %) Group 1, 2/9 (22.2 %) Group 4, and 5/9 (55.6 %) Group 5. CMA confirmed complete CEP17 deletion in one case. CONCLUSIONS: Alternative chromosome 17 markers and/or CMA may be needed to resolve HER2 status in patients with complete deletion of CEP17.
Pan-cancer methylation analysis of circulating cell-free DNA.
Dong W, Lau CH, Li J … +9 more , Huang Z, Li J, Wu W, Chen X, Huang Y, Huang X, Xu M, Zhu H, Ding Y
Cancer Genet · 2025 Sep · PMID 40737714 · Publisher ↗
BACKGROUND: Universal cancer screening based on methylation analysis of circulating cell-free DNA (cfDNA) enables multi-organ cancer detection, thereby reducing all-cause mortality and preventing cancer misdiagnosed by g...
BACKGROUND: Universal cancer screening based on methylation analysis of circulating cell-free DNA (cfDNA) enables multi-organ cancer detection, thereby reducing all-cause mortality and preventing cancer misdiagnosed by guideline-based cancer-specific screening. This study aims to establish a gene methylation panel for blood-based multi-cancer early detection. MATERIALS AND METHODS: Bioinformatics analysis and in-house DNA sequencing of various human cancer cell lines and blood from healthy persons were carried out to identify candidate pan-cancer methylation sites. Methylation-sensitive restriction enzymes-quantitative PCR (MSRE-qPCR) was then used for DNA methylation analysis. Blood cfDNA from 103 patients with diverse cancer types and 40 healthy subjects was extracted for methylation analysis. RESULTS: By bioinformatics analysis and in-house DNA sequencing, we identified two candidates pan-cancer methylation sites, HIST1H4F and CDO1. A long stretch of methylation was found on the promoters of HIST1H4F and CDO1 across various cancer cell lines, while these genomic regions are unmethylated in healthy persons. When tested with clinical samples, the detection sensitivity and specificity of our gene methylation panel in detecting pan-cancer were 47.57 % and 90.00 %, respectively. When analyzed by cancer subtypes, the detection sensitivity was the highest in lung cancer (76.92 %), followed by colorectal cancer (63.64 %) and gastric cancer (50.00 %). CONCLUSIONS: Our newly established gene methylation panel provides an alternative assay for multi-cancer screening tests. As no bisulfite conversion and invasive procedures are required, it can accelerate cancer diagnosis and streamline the operation for pan-cancer screening.
The mechanism of lncRNA SSTR5-AS1 promoting ferroptosis resistance and immune escape in ovarian cancer cells by recruiting STAT3 to regulate SLC7A11 expression.
Wei Q, Yang Y, Wang H … +2 more , Li C, Li Y
Cancer Genet · 2025 Sep · PMID 40716132 · Publisher ↗
OBJECTIVE: Ovarian cancer (OC) is the foremost cause of gynecological cancer-related mortality. Respecting the role of long noncoding RNAs (lncRNAs) in malignancies, we explored the mechanism of SSTR5-AS1 regulating OC c...
OBJECTIVE: Ovarian cancer (OC) is the foremost cause of gynecological cancer-related mortality. Respecting the role of long noncoding RNAs (lncRNAs) in malignancies, we explored the mechanism of SSTR5-AS1 regulating OC cell ferroptosis resistance and immune escape via the signal transducer and activator of transcription 3 (STAT3)/solute carrier family 7a member 11 (SLC7A11) axis. METHODS: OC cells were treated with si-SSTR5-AS1, oe-SSTR5-AS1 and oe-SLC7A11 plasmids. SSTR5-AS1, STAT3 and SLC7A11 mRNA levels, and cell malignant behaviors were assessed by RT-qPCR, CCK-8 and Transwell assays. Fe, glutathione (GSH) and malondialdehyde (MDA) levels in Erastin-induced OC cells, and viability and apoptosis in OC cell-co-cultured CD8T cells were determined using kits, and CCK-8 and flow cytometry. SSTR5-AS1 distribution was detected by subcellular fractionation assay. STAT3 and SLC7A11 protein levels were measured by Western blot. The protein interaction and binding relationship between SSTR5-AS1 and STAT3 were predicted by database and confirmed using RIP and verified using dual-luciferase assays. RESULTS: SSTR5-AS1 was up-regulated in OC cells. SSTR5-AS1 overexpression facilitated OC cell malignant behaviors, down-regulated Fe and MDA levels and up-regulated the GSH level in Erastin-treated OC cells, and diminished viability and enhanced apoptosis in OC cell-co-cultured CD8T cells, suggesting that SSTR5-AS1 overexpression promoted OC cell ferroptosis resistance and immune escape, which were inhibited by its downregulation. SSTR5-AS1 facilitated SLC7A11 transcription and expression by recruiting STAT3. SLC7A11 overexpression partially reversed the effects of SSTR5-AS1 knockdown on OC cells. CONCLUSION: SSTR5-AS1 promoted SLC7A11 transcription and expression by recruiting STAT3, thereby promoting ferroptosis resistance and immune escape of OC cells.
Unraveling prognostic biomarkers in oral squamous cell carcinoma: An approach based on explainable artificial intelligence.
Dogra A, Hasija Y
Cancer Genet · 2025 Sep · PMID 40712338 · Publisher ↗
Oral cancer is among the top malignancies and the leading cause of death worldwide. Poor outcomes are attributed to local recurrence and distant metastasis of disease. There is an urgent need to identify the potential bi...
Oral cancer is among the top malignancies and the leading cause of death worldwide. Poor outcomes are attributed to local recurrence and distant metastasis of disease. There is an urgent need to identify the potential biomarkers that may help in prognostication and management of oral cancer. This study aimed to find potential prognostic biomarkers for oral squamous cell carcinoma (OSCC) using eXplainable artificial intelligence (XAI). After the curation of microarray data from GSE31056 (38 relapsed and 58 non-relapsed OSCC samples/ normal oral tissue samples), the application of XAI on Extreme Gradient Boosting algorithm machine learning (ML) models trained on binary classification datasets was employed. After successfully incorporating SHapley Additive exPlanations values into the ML models, 20 top significant genes associated with the relapse of OSCC were identified. The key genes included FAM49B, TTC39A, IFI16, ANGPTL4, HSPH1, GRIA2, SERF2 and others which contribute crucially to cell growth, cell invasion, apoptosis, disease progression, overall survival and disease-free survival. Further, a network of genes and their targeting microRNAs (miRNAs) revealed that miRNAs hsa-let-7b-5p, hsa-miR-27a-3p and hsa-miR-124-3p, had the highest interactions with genes. The predicted genes and miRNAs might be worthy prognostic markers and open the possibilities to understand the underlying pathways and recognize therapeutic targets for aggressive OSCC.
The KRAS p.Ala146Thr mutation promotes the proliferation of colorectal cancer cells via CDK1-mediated ERK signaling.
Li W, Xu Z, Dong X … +3 more , Yang X, Wang G, He G
Cancer Genet · 2025 Sep · PMID 40706337 · Publisher ↗
KRAS is the most frequently mutant human oncogene, with mutations present in more than 30% of colorectal cancer (CRC) cases. A rare somatic mutation in KRAS, NM_004985.5 : c.436G>A (p.Ala146Thr), was identified in carcin...
KRAS is the most frequently mutant human oncogene, with mutations present in more than 30% of colorectal cancer (CRC) cases. A rare somatic mutation in KRAS, NM_004985.5 : c.436G>A (p.Ala146Thr), was identified in carcinoma tissues from two CRC patients using Sanger sequencing. An alternative transcript of CDC37 was identified that retained intron 3. No splicing variant was detected within the coding exons and exon-intron boundaries of CDC37. The transcript encoded both truncated and full-length CDC37 proteins. Furthermore, KRAS, CDC37 and HSP90 interacted with each other. The expression levels of HSP90 and CDC37 in carcinoma tissues with the KRAS p.Ala146Thr mutation were higher than those in para-carcinoma tissues. Notably, the p.Ala146Thr mutation significantly upregulated the expression of CDK1, which in turn promoted CRC cell proliferation through activation of ERK signaling. These findings uncover a novel molecular mechanism underlying CRC pathogenesis associated with the KRAS p.Ala146Thr mutation and provide potential insights for developing targeted therapies for this subset of CRC.
Detection of VHL variant on multigene panel testing for hereditary breast cancer: Implications for genetic counselling.
Ling JY, Stephenson KA, Romanuik TL … +3 more , Thibodeau ML, Soleimani M, Paton KE
Cancer Genet · 2025 Sep · PMID 40694912 · Publisher ↗
As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breas...
As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the VHL gene variant without other cancer risk alleles (e.g., BRCA1/BRCA2) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.
The effect of HOTAIR gene variants on the development of bladder cancer and its clinicopathological characteristics in a Caucasian population.
Akkoç Y, Sulhan H, Akgöllü E … +1 more , Çift A
Cancer Genet · 2025 Sep · PMID 40684544 · Publisher ↗
BACKGROUND: The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the HOTAIR gene have been shown to promote tumor...
BACKGROUND: The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the HOTAIR gene have been shown to promote tumor progression in many cancers. rs874945 and rs4759314 polymorphisms in the HOTAIR gene cause changes in the expression levels of lncRNAs synthesized from this gene. The aim of this study was to explore for the first time the association of these variants with BC in a Caucasian population. METHODS: The present study explored the HOTAIR gene polymorphisms in 98 BC patients and in 150 healthy individuals using real-time polymerase chain reaction (RT-PCR). RESULTS: Carrying rs874945 G allele and GA genotype increased the BC risk in the statistic models. However, even if rs4759314 variant increased of BC risk was not significant. Similarly, although both polymorphisms increased clinicopathological features associated with poor prognosis, they were not statistically significant. Moreover, being older than 60 years and smoking are independent risk factors for BC. DISCUSSION: The current study is the first to show that patients carrying the G allele of the rs874945 polymorphism have a higher risk of BC in the Caucasian population. This work suggests that rs4759314 polymorphism should be studied in the Caucasian population with a larger sample size of BC patients.
Corrigendum to "Ultra-sensitive detection of melanoma NRAS mutant ctDNA based on programmable endonucleases" [Cancer Genetics 294-295 (2025) 47-56].
Zhang Z, Ji Q, Zhang Z … +6 more , Lyu B, Li P, Zhang L, Chen K, Fang M, Song J
Cancer Genet · 2025 Sep · PMID 40684543 · Publisher ↗
Abstract loading — click title to view on PubMed.
Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach.
Kim J, Jang HL, Hong JY … +7 more , Kim ST, Park SH, Park JO, Kim KM, Geun Kim D, Lee J, Lim SH
Cancer Genet · 2025 Sep · PMID 40682921 · Publisher ↗
BACKGROUND: 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 PIK3CA gene. Recent advancements have shown eff...
BACKGROUND: 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 PIK3CA gene. Recent advancements have shown effective treatment for patients with PIK3CA-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. METHODS: 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 PIK3CA 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. RESULTS: Among the 3886 patients, PIK3CA mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring PIK3CA 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, p = 0.001). In contrast, PIK3CA 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. CONCLUSION: Of 3886 patients with metastatic solid tumors, 358(9.2 %) had PIK3CA mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.
Tandem duplication and triplication in BRCA1: revisiting the large genomic rearrangements via optical genome mapping.
Allister BA, Lühmann JL, Wendeburg L … +8 more , Dechend F, Beger C, Tölle S, von Ehr J, Ripperger T, Auber B, di Donato N, Steinemann D
Cancer Genet · 2025 Sep · PMID 40664023 · Publisher ↗
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...
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 BRCA1, 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 BRCA1 exon 18-19 is predicted to generate a premature termination codon, namely p.(His1732Metfs*10). The triplication of BRCA1 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.
Upregulation of Uracil DNA Glycosylase (UNG) in Prostate Cancer.
Rouhi V, Habibi S, Koseoglu DH … +2 more , Ari DE, Guven M
Cancer Genet · 2025 Sep · PMID 40652631 · Publisher ↗
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 signif...
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 (p = 0.02). OGG1 expression also increased by 2.60-fold, but this was not statistically significant (p > 0.05). A positive correlation was observed between UNG expression and PSA levels in tumor tissues (r = 0.341, p = 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.
Influence of IL-38 as a novel biomarker on the pathophysiological processes of esophageal cancer.
Zeng D, Ye S, Yin W … +2 more , Lian D, Zhou S
Cancer Genet · 2025 Sep · PMID 40651313 · Publisher ↗
OBJECTIVE: This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer. METHODS: Differential protein expression between esophageal tumor tissue and adjacent...
OBJECTIVE: This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
TFAP2E acts as a tumor suppressor by regulating cell cycle progression in oral squamous cell carcinoma cells.
Sakai R, Inagaki Y, Tsurumi H … +4 more , Ohashi A, Takayama T, Sato S, Fujiwara K
Cancer Genet · 2025 Sep · PMID 40651312 · Publisher ↗
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. TFAP...
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. TFAP2E 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 TFAP2E 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.
ADAR1 gene expression and its importance in breast cancer.
Tekin B, Ekizoglu S, Kaya SB … +2 more , Guven M, Trabulus DC
Cancer Genet · 2025 Sep · PMID 40627891 · Publisher ↗
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 t...
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, p < 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, p < 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 (p = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (p = 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.
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