Cancer Genetics[JOURNAL]
Sun
200 papers
The mechanism of E3 ubiquitin ligase HERC1 regulating ferroptosis in lung adenocarcinoma cells.
Ye F, Xu Y, Zhu X … +4 more , Ding Q, Wang Y, Lu S, Chen Y
Cancer Genet · 2025 Apr · PMID 39983667 · Publisher ↗
OBJECTIVE: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer. Herein, we probed into the role of E3 ubiquitin protein ligase family member 1 (HERC1) in promoting ferroptosis and inhibiting LUAD cell...
OBJECTIVE: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer. Herein, we probed into the role of E3 ubiquitin protein ligase family member 1 (HERC1) in promoting ferroptosis and inhibiting LUAD cell proliferation by regulating RAF proto-oncogene serine/threonine-protein kinase (C-RAF). METHODS: In cultured human normal lung epithelial cells and non-small cell lung adenocarcinoma cell lines, HERC1 expression was determined by RT-qPCR and Western blot tests. PC-9 and Calu-3 cells were transfected with oe-HERC1, oe-C-RAF or their negative controls. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe levels were assessed by biochemical assays. Cell viability, death, and proliferation were evaluated by CCK-8, LDH and colony formation assays, followed by assessments of HERC1-C-RAF interaction, C-RAF ubiquitin level, and C-RAF protein stability. RESULTS: HERC1 was poorly expressed in LUAD cells. HERC1 promoted LUAD cell ferroptosis and repressed their proliferation and migration, corresponding to reduced levels of system xc-, GPX4, and GSH, as well as elevated levels of ROS, MDA, Fe, and ACSL4. LUAD cells overexpressing HERC1 displayed decreased C-RAF protein level, HERC1-C-RAF interaction, elevated C-RAF ubiquitin level, and accelerated C-RAF protein degradation, indicating that HERC1 facilitated C-RAF ubiquitin degradation and attenuated C-RAF protein stability via interaction with C-RAF. C-RAF overexpression partially abrogated the regulatory impact of HERC1 on LUAD cell ferroptosis and proliferation. CONCLUSION: HERC1 expedites C-RAF ubiquitin degradation by interacting with C-RAF, which consequently promotes ferroptosis, thereby inhibiting LUAD cell proliferation.
MYC-r with a non-IG partner concurrently with a cryptic t(12;21) in B-lymphoblastic leukemia: A case and prognostic significance.
Koduru P, Chen W, Fuda F … +2 more , Pacheco M, Garcia R
Cancer Genet · 2025 Apr · PMID 39983666 · Publisher ↗
B-lymphoblastic leukemia (B-ALL) in children is characterized by recurrent chromosomal rearrangements that mostly have prognostic value. MYC rearrangements (MYC-r), typically associated with Burkitt lymphoma or mature B-...
B-lymphoblastic leukemia (B-ALL) in children is characterized by recurrent chromosomal rearrangements that mostly have prognostic value. MYC rearrangements (MYC-r), typically associated with Burkitt lymphoma or mature B-cell neoplasms are infrequent in B-ALL. We report here a unique case of childhood B-ALL with concurrent MYC-r with a non-IG partner and a cryptic t(12;21). Leukemic cells had lymphoblastic morphology. Immunophenotypically, leukemic blasts were CD10 (+, slightly bright), CD15 (few +), CD19 (+), CD20 (+, partial), CD22 (+), CD34 (-), CD38 (+, slightly variably), CD45 (+, partial), cytoplasmic CD79a (+), HLA-DR (+), surface Ig (-), MPO (-), and TdT (+, partially). This immunophenotype was consistent with B-ALL. Cytogenetically, the karyotype was complex including a t(4;8)(q31;q24), and FISH analysis showed MYC-r, ETV6::RUNX1 and loss of ETV6 allele. The patient has been in complete remission for 11 years following the diagnosis. We reviewed cases of B-ALL with double leukemogenic alterations and MYC-r with non-IG partners to understand the clinical outcome in these rare patients.
Integrating radiomics and gene expression by mapping on the image with improved DeepInsight for clear cell renal cell carcinoma.
Kawahara D, Kishi M, Kadooka Y … +2 more , Hirose K, Murakami Y
Cancer Genet · 2025 Apr · PMID 39983665 · Publisher ↗
BACKGROUND: Radiomics analysis extracts high-dimensional features from medical images, which are used to predict outcomes in machine learning (ML). Recently, deep-learning methods have become applicable to image data con...
BACKGROUND: Radiomics analysis extracts high-dimensional features from medical images, which are used to predict outcomes in machine learning (ML). Recently, deep-learning methods have become applicable to image data converted from nonimage samples. PURPOSE: This study conducted a comparative analysis of outcome-prediction performance using radiomics with a conventional ML approach and deep-learning (DL) approach utilising DeepInsight. Furthermore, we enhance the DeepInsight model by integrating radiomics features with gene expression data. This integration aims to improve predictive power and provide a more comprehensive understanding of ccRCC, ultimately contributing to more personalized and effective treatment strategies. METHODS: A total of 142 patients with clear cell renal cell carcinoma who underwent surgery were divided into training and test datasets. Radiomics features were extracted in the entire tumour region from CT images. The two-year disease-free survival was predicted using ML and DL. ML was used for selective features after LASSO regression. ML algorithms were employed for classification, including the support vector machine, k-nearest neighbour, and neural network classifiers. For DL, radiomics features and gene-expression data were converted into image data with DeepInsight, and classification tasks were performed with DL techniques such as AlexNet, SqueezeNet, and InceptionNet. RESULTS: For ML, 17 prognosis-related radiomic features were selected from the LASSO regression. The ML accuracy was 76.5 %, 71.4 %, and 78.1 % for the support vector machine, k-nearest neighbour, and neural network models, respectively. For DL, the accuracies were 76.7 %, 83.1 %, and 85.4 % for AlexNet, SqueezeNet, and InceptionNet, respectively. Furthermore, the integrated DeepInsight models exhibited the highest accuracy of 90.9 %. CONCLUSION: The proposed DL approach utilising DeepInsight demonstrated a significant improvement in outcome-prediction performance compared with the conventional ML approach. Furthermore, the integration of DL with radiomics features and gene-expression data effectively captures the relationship between biological information and image data, rendering it a promising tool for enhancing outcome-prediction capabilities.
Three FGFR4 gene polymorphisms contribute to the susceptibility of urethral cancer in the middle and south of Iraq population.
Jameel ZI
Cancer Genet · 2025 Apr · PMID 39970854 · Publisher ↗
BACKGROUND: Urothelial cell carcinoma is quite prevalent, making up close to 90 % of all cases. Men are more likely to suffer from it than women, and it mostly affects the elderly. Fibroblast growth factor receptor 4 (FG...
BACKGROUND: Urothelial cell carcinoma is quite prevalent, making up close to 90 % of all cases. Men are more likely to suffer from it than women, and it mostly affects the elderly. Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cell proliferation and cancer progression. AIM: this study was conducted to assess the association between FGFR4 gene polymorphism and the risk of Urothelial Cell Carcinoma in Iraq. METHODS: genomic DNA samples were extracted from a total 200 samples of blood. Three primers were designed to enhance three commonly observed genetic variation, rs2011077, rs351855, and rs1966265. The single strand conformation polymorphisms technique (SSCP) was genotyped and confirmed by further sequencing protocols. RESULTS: The results of this study show that cases with the G/A variant of the rs351855 genotype have a marked increase in risk to Urothelial Cell Carcinoma (P = 0.001, OR 0.32, 95 % CI 0.20 to 0.94). Cases with genotype rs2011077: T\C has also associated with the increased the risk of UCC (P = 0.001, OR= 0.50, 95 % CI = 0.33 to 0.76). The Linkage Disequilibrium revealed a significant relationship between the T allele of the rs2011077 locus and the A allele of the rs351855 locus, leading to the formation of the T\A haplotype in cases diagnosed with the UCC. Our results show that FGFR4 gene polymorphisms (rs351855 and rs2011077) have significant associations with increased risk of Urothelial Cell Carcinoma. CONCLUSION: current study indicates that the specific polymorphisms have proven to be promising as a major genetic marker for identifying cases who may be more susceptible to diagnosis and recurrence Urothelial Cell Carcinoma.
Novel Co-frameshift mutations in N- and C-terminal regions of CEBPA in acute myeloid leukemia: A case report.
Mousaei Ghasroldasht M, Hosseinabadi SV, Askari RE … +1 more , Lotfalipour R
Cancer Genet · 2025 Apr · PMID 39961276 · Publisher ↗
Acute myeloid leukemia (AML) is a hematologic malignancy marked by abnormal myeloid cell proliferation or differentiation arrest in the bone marrow. AML prognosis is influenced by genetic mutations, including in NPM1, FL...
Acute myeloid leukemia (AML) is a hematologic malignancy marked by abnormal myeloid cell proliferation or differentiation arrest in the bone marrow. AML prognosis is influenced by genetic mutations, including in NPM1, FLT3-ITD, cKIT, and CEBPA genes. CEBPA, located on chromosome 19q13.11, is critical for myeloid differentiation in the hematopoietic system, and mutations in this gene occur in about 10-15 % of de novo AML cases. These mutations often appear as frameshift alterations in the N-terminal or in-frame insertions/deletions in the C-terminal basic leucine zipper (bZIP) domain. We report a unique CEBPA mutation profile in a 19-year-old male with AML, normal karyotype, and no mutations in FLT3-ITD, NPM1, or cKIT. The patient exhibited a frameshift mutation in the N-terminal region and a novel in-frame duplication in the C-terminal regions of CEBPA, which has not been previously reported in AML. This case emphasizes the importance of genetic profiling in identifying clinically relevant mutation patterns and highlights the potential of genetic insights to inform personalized treatment. It also underscores the need for further studies on the functional implications of unique CEBPA mutations in AML pathogenesis.
De novo RUNX1-driven acute myeloid leukemia requiring integrative genetics.
Eno CC, Lorber J, Vail E … +1 more , Schreck R
Cancer Genet · 2025 Apr · PMID 39923644 · Publisher ↗
Copy number variants are common in myeloid malignancies and may hold diagnostic, prognostic or therapeutic significance. We present a case of acute myeloid leukemia driven by a RUNX1 deletion with no prior history of a m...
Copy number variants are common in myeloid malignancies and may hold diagnostic, prognostic or therapeutic significance. We present a case of acute myeloid leukemia driven by a RUNX1 deletion with no prior history of a myeloid neoplasm. Discovery of the underlying genetic lesion required multiple testing platforms highlighting the strengths and weaknesses of each test type. Additionally, this case adds to the literature of RUNX1 deletion AML, the adverse prognosis that these cases share and the potential consideration of RUNX1 alterations (both deletions and mutations) as a specific AML entity.
Clinical and genetic characteristics in two cases of Birt-Hogg-Dubé syndrome associated with papillary renal cell carcinoma and rare Folliculin (FLCN) variants.
Evans MG, Thomas LW, Nakasaki M … +6 more , Charifa A, Sisk A, Liu S, Kuklinski LF, Shuch B, Quintero-Rivera F
Cancer Genet · 2025 Apr · PMID 39893707 · Publisher ↗
Birt-Hogg-Dubé syndrome (BHDS) is characterized by autosomal dominant alterations in the Folliculin (FLCN) gene, resulting in cutaneous, pulmonary, and renal abnormalities. In particular, affected individuals are suscept...
Birt-Hogg-Dubé syndrome (BHDS) is characterized by autosomal dominant alterations in the Folliculin (FLCN) gene, resulting in cutaneous, pulmonary, and renal abnormalities. In particular, affected individuals are susceptible to the development of renal cell carcinoma (RCC), which most frequently present as chromophobe tumors or hybrid cancers with features of oncocytoma and chromophobe RCC. Type 1 and type 2 papillary neoplasms have rarely been described in the setting of BHDS, and we present two additional cases. Utilizing next-generation sequencing, the patients were found to harbor germline FLCN variants that are not well-documented in the medical literature. While RCCs associated with BHDS are thought to portend a better prognosis compared to their non-syndromic counterparts, the patients described here experienced variable clinical outcomes-one developed locally aggressive disease, distant metastases, and quickly succumbed to his disease.
False positive NUP98 fluorescence in situ hybridization rearrangements in B-acute lymphoblastic leukemia.
Gagnon MF, Tonk SS, Carcamo B … +15 more , Bustamante D, Stein M, Johnson SH, Vasmatzis G, Zepeda-Mendoza CJ, Greipp PT, Xu X, Ketterling RP, Peterson JF, Wang W, Liu YJ, Tonk V, Tsuchiya K, Chavali S, Baughn LB
Cancer Genet · 2025 Apr · PMID 39892372 · Publisher ↗
Gene fusions involving NUP98 have been reported in several hematologic malignancies yet have been very rarely reported in B-acute lymphoblastic leukemia (B-ALL). Two cases of B-ALL for which chromosome banding analysis (...
Gene fusions involving NUP98 have been reported in several hematologic malignancies yet have been very rarely reported in B-acute lymphoblastic leukemia (B-ALL). Two cases of B-ALL for which chromosome banding analysis (CBA) and fluorescence in situ hybridization (FISH) suggested apparent NUP98 rearrangements were further investigated with next-generation sequencing-based methodologies to verify the findings obtained with traditional cytogenetic methodologies. In the first case, CBA revealed a hyperdiploid karyotype with multiple structural abnormalities including additional material of unknown origin at 11p15; subsequent break-apart probe (BAP) FISH for NUP98 demonstrated 2 intact fusion signals and a single separate 5'NUP98 signal. However, whole-genome sequencing found no evidence of a NUP98 gene fusion. The results obtained with conventional cytogenetic methodologies were in fact attributable to structural variants (SV) with breakpoints not within NUP98 but within the 5'NUP98 BAP probe-binding sequence. In the second case, CBA revealed several structural and numeric abnormalities including a complex translocation between chromosomes 11 (at 11p15.4) and 19 (at 19p13.3) and an insertion of unknown material at 11p15.4. BAP FISH demonstrated a typical FISH signal pattern consistent with an apparent NUP98 rearrangement. However, no evidence of a NUP98 fusion was found on RNA sequencing. In conclusion, the two cases thus presented with clinical false positive NUP98 rearrangements by FISH. In the clinical laboratory, SVs in the vicinity of genes involved in recurrent rearrangements in hematologic malignancies may result in misleading results with conventional chromosome methodologies. This may preclude an accurate definition of the genetic attributes of malignancies with ensuing impacts on risk stratification and management. Higher-resolution testing methodologies such as whole-genome sequencing and RNA sequencing may be helpful in resolving unexpected results with conventional chromosome methodologies and enhancing the accuracy of genetic characterization of hematological malignancies in the clinical laboratory.
In silico protein structural analysis of PRMT5 and RUVBL1 mutations arising in human cancers.
Al-Marrawi M, Petreaca RC, Bouley RA
Cancer Genet · 2025 Apr · PMID 39874873 · Full text
DNA double strand breaks (DSBs) can be generated spontaneously during DNA replication and are repaired primarily by Homologous Recombination (HR). However, efficient repair requires chromatin remodeling to allow the reco...
DNA double strand breaks (DSBs) can be generated spontaneously during DNA replication and are repaired primarily by Homologous Recombination (HR). However, efficient repair requires chromatin remodeling to allow the recombination machinery access to the break. TIP60 is a complex conserved from yeast to humans that is required for histone acetylation and modulation of HR activity at DSBs. Two enzymatic activities within the TIP60 complex, KAT5 (a histone acetyltransferase) and RUVBL1 (an AAA+ ATPase) are required for efficient HR repair. Post-translational modification of RUVBL1 by the PRMT5 methyltransferase activates the complex acetyltransferase activity and facilitates error free HR repair. In S. pombe a direct interaction between PRMT5 and the acetyltransferase subunit of the TIP60 complex (KAT5) was also identified. The TIP60 complex has been partially solved experimentally in both humans and S. cerevisiae, but not S. pombe. Here, we used in silico protein structure analysis to investigate structural conservation between S. pombe and human PRMT5 and RUVBL1. We found that there is more similarity in structure conservation between S. pombe and human proteins than between S. cerevisiae and human. Next, we queried the COSMIC database to analyze how mutations occurring in human cancers affect the structure and function of these proteins. Artificial intelligence algorithms that predict how likely mutations are to promote cellular transformation and immortalization show that RUVBL1 mutations should have a more drastic effect than PRMT5. Indeed, in silico protein structural analysis shows that PRMT5 mutations are less likely to destabilize enzyme function. Conversely, most RUVBL1 mutations occur in a region required for interaction with its partner (RUVBL2). These data suggests that cancer mutations could destabilize the TIP60 complex. Sequence conservation analysis between S. pombe and humans shows that the residues identified in cancer cells are highly conserved, suggesting that this may be an essential process in eukaryotic DSB repair. These results shed light on mechanisms of DSB repair and also highlight how S. pombe remains a great model system for analyzing DSB repair processes that are tractable in human cells.
Exploring the role of transcription factor TWIST1 in bladder cancer progression.
El Azzouzi M, Addoum B, El Ahanidi H … +9 more , Hassan I, Tetou M, Ameur A, Al Bouzidi A, Oukabli M, Benbacer L, Attaleb M, El Mzibri M, Chaoui I
Cancer Genet · 2025 Apr · PMID 39870050 · Publisher ↗
The transcription factor TWIST1 is a major regulator of Epithelial-Mesenchymal Transition, enhancing cancer cell mobility and invasive potential. Overexpression of TWIST1 is associated with tumor progression and poor pro...
The transcription factor TWIST1 is a major regulator of Epithelial-Mesenchymal Transition, enhancing cancer cell mobility and invasive potential. Overexpression of TWIST1 is associated with tumor progression and poor prognosis. In our study, we explored the role of TWIST1 as both a prognostic biomarker and a therapeutic target in bladder cancer (BC), as well as the relationship between its promoter methylation and mRNA expression in bladder cancer patients. In cohort of 66 bladder cancer patients, we explored TWIST1 expression levels in tumor samples through RT-qPCR analysis; Our findings revealed a significant correlation between high TWIST1 expression levels and advanced bladder tumor stages, grades, and progression; suggesting its association with aggressive BC phenotypes. Importantly, patients with low TWIST1 expression exhibited significantly prolonged disease-free survival (DFS), indicating its potential as a prognostic marker for stratification and as a therapeutic target in advanced BC. In contrast, there was no direct correlation between TWIST1 promoter methylation status and TWIST1 expression levels in BC tumors. In summary, TWIST1 expression could play an important role as a molecular marker for BC patients' prognosis and overall survival prediction. Moreover, our results suggest that TWIST1 promoter methylation doesn't affect the gene expression in BC. Furthermore, understanding the molecular mechanisms driving TWIST1 dysregulation may uncover novel therapeutic targets to improve the management of BC.
A novel POT1-TPD presentation: A germline pathogenic POT1 variant discovered in a patient with newly diagnosed posterior fossa ependymoma.
Gilene S, Knapke S, Leino D … +2 more , Roy S, Raskin S
Cancer Genet · 2025 Apr · PMID 39864275 · Publisher ↗
INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently r...
INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently reported malignancies [1]. Protection of telomeres protein 1 (POT1) is part of the shelterin protein complex to maintain/protect telomeres [2]. Proposed mechanisms for oncogenesis with POT1 loss of function include telomere elongation and DNA damage response causing genomic instability [3]. Ependymomas are a heterogeneous group representing one-third of pediatric brain tumors and are locally aggressive with frequent recurrence [4]. CASE PRESENTATION: A healthy 3-year-old male presented with worsening vertigo, headaches, and emesis. Radiographic studies demonstrated a midline posterior fossa mass in the fourth ventricle. Following a gross total resection, pathology demonstrated a posterior fossa ependymoma, group A. Next generation sequencing (NGS) using our institution's clinically validated panel, "CinCSeq," identified a POT1 splice site variant (c.1164-1G>A; variant allele fraction 46 %). Paired germline testing via the Molecular Characterization Initiative confirmed this variant as heterozygous in the patient. Genetic testing confirmed the POT1 pathogenic variant in his mother, who has a history of multiple nevi. The patient completed treatment with focal proton radiotherapy with no evidence of disease recurrence to date. DISCUSSION: To our knowledge, this represents the first documented pediatric ependymoma patient with a familial, germline POT1 pathogenic variant. Somatic POT1 mutational frequency, as determined by NGS in over 60,000 solid tumors, is 2.94 %. Among this cohort, 48 cases were ependymomas with one non-benign POT1 mutation [5]. Alterations of telomere maintenance have been reported in intracranial ependymomas previously through increased human telomerase reverse transcriptase (hTERT) expression [6,7]. This case sheds light on a potential new predisposition for ependymoma development and the expanding phenotype of POT1-TPD. We recognize the POT1 pathogenic variant may have been discovered incidentally in this case. Further research is needed to advance our understanding of the association between POT1 genetic alterations and ependymomas.
Hepatoblastoma in a patient with neurofibromatosis type 1: A case report.
Praga A, Hirsch TZ, Vidaud D … +6 more , Laithier V, Puzenat E, Zucman-Rossi J, Mussini C, Kuentz P, Piard J
Cancer Genet · 2025 Apr · PMID 39862580 · Publisher ↗
BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genodermatoses. It can affect every organ and is associated with an increased risk of benign and malignant tumors. Most common tumoral locations involv...
BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genodermatoses. It can affect every organ and is associated with an increased risk of benign and malignant tumors. Most common tumoral locations involve nervous system and soft tissues but a large variety of tumors have been described. So far, hepatoblastoma in a patient with NF1 has been reported twice in the literature. CASE PRESENTATION: A liver mass was discovered in a 11 year-old girl with NF1 leading to a diagnosis of epithelial hepatoblastoma with pulmonary metastasis. Targeted analysis on blood revealed a germline NF1 missense variant. Exome sequencing, RNA-seq and methylation analyses performed on tumoral and metastatic samples confirmed the germline NF1 variant and showed classical driver variants for hepatoblastoma. CONCLUSIONS: We present here the third case of hepatoblastoma in a patient with NF1 and discuss the possible link between this rare tumor and this neurocutaneous genetic condition.
Occult collision tumor of the gastroesophageal junction comprising adenocarcinomas with distinct molecular profiles.
Blaszczyk MB, Boukhar SA, Zhou Z … +3 more , Berim L, Ganesan S, Riedlinger GM
Cancer Genet · 2025 Apr · PMID 39805155 · Publisher ↗
Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic t...
Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction. Biopsy of the esophageal portion of the GEJ mass showed a mismatch repair deficient tumor with loss of immunoreactivity for MLH1 and PMS2, while the biopsy taken from the gastric portion of the mass revealed a separate tumor with a discordant, non-overlapping, set of molecular alterations, including an EML4::ALK fusion, as well as intact MMR. This case illustrates one way in which NGS can reveal diagnoses such as collision tumor that are wholly unexpected based on clinical and histological grounds. Such diagnoses can have important implications for patient care, particularly in cases where there is discordance for targetable molecular alterations.
Omics approaches: Role in acute myeloid leukemia biomarker discovery and therapy.
Shafiei FS, Abroun S, Vahdat S … +1 more , Rafiee M
Cancer Genet · 2025 Apr · PMID 39798496 · Publisher ↗
Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has the highest fatality rate. Patients aged 65 and above exhibit the poorest prognosis, with a mere 30 % survival rate within one year. One im...
Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has the highest fatality rate. Patients aged 65 and above exhibit the poorest prognosis, with a mere 30 % survival rate within one year. One important issue in optimizing outcomes for AML patients is their limited ability to predict responses to specific therapies, response duration, and likelihood of relapse. Despite rigorous therapeutic interventions, a significant proportion of patients experience relapse. Consequently, there is a pressing need to introduce new targets for therapy. Sequencing and biotechnology have come a long way in the last ten years. This has made it easier for many omics technologies, like genomics, transcriptomics, proteomics, and metabolomics, to study molecular mechanisms of AML. An integrative approach is necessary to understand a complex biological process fully and offers an important opportunity to understand the information underlying diseases. In this review, we studied papers published between 2010 and 2024 employing omics approaches encompassing diagnosis, prognosis, and risk stratification of AML. Finally, we discuss prospects and challenges in applying -omics technologies to the discovery of novel biomarkers and therapy targets. Our review may be helpful for omics researchers who want to study AML from different molecular aspects.
Prognosis prediction and drug guidance of ovarian serous cystadenocarcinoma through mitochondria gene-based model.
Shen D, Wu C, Chen M … +5 more , Zhou Z, Li H, Tong X, Chen Z, Guo Y
Cancer Genet · 2025 Apr · PMID 39754905 · Publisher ↗
BACKGROUND: Mitochondrial dysregulation contributes to the chemoresistance of multiple cancer types. Yet, the functions of mitochondrial dysregulation in Ovarian serous cystadenocarcinoma (OSC) remain largely unknown. AI...
BACKGROUND: Mitochondrial dysregulation contributes to the chemoresistance of multiple cancer types. Yet, the functions of mitochondrial dysregulation in Ovarian serous cystadenocarcinoma (OSC) remain largely unknown. AIM: We sought to investigate the function of mitochondrial dysregulation in OSC from the bioinformatics perspective. We aimed to establish a model for prognosis prediction and chemosensitivity evaluation of the OSC patients by targeting mitochondrial dysregulation. METHODS: Differentially expressed genes (DEGs) were screened from the Cancer Genome Atlas (TCGA)-OV dataset and the mitochondrial-related DEGs were identified from the Human MitoCarta 3.0 database. Prognosis-related mitochondria-related genes (MRGs) were screened to establish the MRGs-based risk score model for prognosis prediction. To validate the risk score model, the risk score model was then evaluated by IHC staining intensity and survival curves from clinical specimens of OSC patients. Migration and proliferation assays were performed to elucidate the role of carcinogenic gene ACSS3 in serous ovarian cancer cell lines. RESULTS: Using consensus clustering algorithm, we identified 341 MRGs and two subtypes of OSC patients. Moreover, we established a novel prognostic risk score model by combining the transcription level, intensity and extent scores of MRGs for prognosis prediction purpose. The model was established using 7 MRGs (ACOT13, ACSS3, COA6, HINT2, MRPL14, NDUFC2, and NDUFV2) significantly correlated to the prognosis of OSC. Importantly, by performing the drug sensitivity analysis, we found that the OSC patients in the low-risk group were more sensitive to cisplatin, paclitaxel and docetaxel than those in the high-risk group, while the latter ones were more sensitive to VEGFR inhibitor Axitinib and BRAF inhibitors Vemurafenib and SB590885. In addition, patients in the low-risk group were predicted to have better response in anti-PD-1 immunotherapy than those in the high-risk group. The risk score model was then validated by survival curves of high-risk and low-risk groups determined by IHC staining scores of OSC clinical samples. The carcinogenic effect of ACSS3 in OSC was confirmed through the knockdown of ACSS3 in SKOV3 and HO-8910 cells. CONCLUSION: To summarize, we established a novel 7 MRGs - based risk score model that could be utilized for prognosis prediction and chemosensitivity assessment in OSC patients.
Analysis of nuclear receptor expression in head and neck cancer.
Mortensen L, Koenigsberg CK, Kimbrough TG … +5 more , Ping J, Adeva GS, Wuertz BR, Gaffney P, Ondrey FG
Cancer Genet · 2025 Jan · PMID 39754894 · Full text
OBJECTIVE: Studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated the importance of nuclear receptors and their associated coregulators in the development and treatment of HNSCC. We sought to c...
OBJECTIVE: Studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated the importance of nuclear receptors and their associated coregulators in the development and treatment of HNSCC. We sought to characterize members of the nuclear receptor super family through interrogation of RNA-Seq and microarray data. MATERIALS AND METHODS: TCGA RNA-Seq data within the cBioportal platform comparing HNSCC samples (n = 515 patients with RNA-Seq data) to normal tissue (n = 82 patients) was interrogated for significant differences in nuclear receptor expression. Affymetrix microarray analysis of HNSCC tumors relative to normal oral mucosa (41 tumor, 13 normal) was analyzed. RESULTS: Of the 48 NR genes and 19 NR cofactors examined, 99 % of tumor samples in the TCGA had some form of NR gene 'alteration' compared to normal tissue. These alterations predominantly encompass expression changes. NR genes (PPARG) and (RORC), and the NR cofactor, (NCOA1), were differentially expressed and downregulated in tumors compared to normal tissue. CONCLUSION: We have discovered significant decreases in PPARG expression with co-occurring changes in genes involved with lipid metabolism and cell cycle progression in HNSCC. We are targeting PPARγ with thiazolidinediones in a series of clinical trials to restore normal signaling via differentiation to hopefully reverse carcinogenesis. We also observed several receptors with differential expression associated with clinical factors that may become the focus of interest in future targeting efforts. These data provide evidence for nuclear receptors playing a role in the dysregulation of gene expression in HNSCC and illustrate the utility of current bioinformatic tools for interrogating complex, high throughput data sets.
Machine learning analysis of CD4+ T cell gene expression in diverse diseases: insights from cancer, metabolic, respiratory, and digestive disorders.
Liao H, Ma Q, Chen L … +7 more , Guo W, Feng K, Bao Y, Zhang Y, Shen W, Huang T, Cai YD
Cancer Genet · 2025 Jan · PMID 39729927 · Publisher ↗
CD4 T cells play a pivotal role in the immune system, particularly in adaptive immunity, by orchestrating and enhancing immune responses. CD4 T cell-related immune responses exhibit diverse characteristics in different d...
CD4 T cells play a pivotal role in the immune system, particularly in adaptive immunity, by orchestrating and enhancing immune responses. CD4 T cell-related immune responses exhibit diverse characteristics in different diseases. This study utilizes gene expression analysis of CD4 T cells to classify and understand complex diseases. We analyzed the dataset consisting of samples from various diseases, including cancers, metabolic disorders, circulatory and respiratory diseases, and digestive ailments, as well as 53 healthy controls. Each sample contained expression data for 22,881 genes. Four feature ranking algorithms, incremental feature selection method, synthetic minority oversampling technique, and four classification algorithms were utilized to pinpoint essential genes, extract classification rules and build efficient classifiers. The following analysis focused on genes across rules, such as AK4, CALU, LINC01271, and RUSC1-AS1. AK4 and CALU show fluctuating levels in diseases like asthma, Crohn's disease, and breast cancer. The analysis results and existing research suggest that they may play a role in these diseases. LINC01271 generally has higher expression in conditions including asthma, Crohn's disease, and diabetes. RUSC1-AS1 is more expressed in chronic diseases like asthma and Crohn's, but less in acute illnesses like tonsillitis and influenza. This highlights the distinct roles of these genes in different diseases. Our approach highlights the potential for developing novel therapeutic strategies based on the transcriptional profiles of CD4 T cells.
Genetic analysis uncovers potential mechanisms linking juvenile ldiopathic arthritisto breast cancer: A Bioinformatic Pilot study.
Jiang J, Yin B, Luo X … +2 more , Chen Y, Wei C
Cancer Genet · 2025 Jan · PMID 39729926 · Publisher ↗
BACKGROUND: In recent years, concerns have emerged regarding the potential link between Juvenile idiopathic arthritis (JIA) and an elevated risk of developing breast cancer. However, the potential relationship between JI...
BACKGROUND: In recent years, concerns have emerged regarding the potential link between Juvenile idiopathic arthritis (JIA) and an elevated risk of developing breast cancer. However, the potential relationship between JIA and breast cancer is currently unclear. The objective of this study is to investigate the mechanism of JIA on cancer risk. METHODS: Use the Bulk-seq data related to JIA, selected from the GEO database, to explore potential candidate genes using methods such as WGCNA and consensus machine learning labeling. Verify using breast cancer Bulk-seq data from TCGA and scRNA-seq analyses. RESULTS: A total of 2050 genes potentially related to JIA were identified by WGCNA, and after merged with differentially expressed genes, 43 potential candidate genes were found. Subsequently, consensus machine learning label analysis was conducted on the aforementioned genes, and a total of 6 genes closely related to JIA were identified. In breast cancer, we found that PRRG4, NCR3 and CREB5 also had significant differences in TCGA. And it is closely related to prognosis. ScRNA-seq analysis showed that the expression of PRRG4 was different in T cells in JIA, and PRRG4 was mainly expressed in T cells in breast cancer. CONCLUSIONS: The findings of this study support a mechanism between JIA and an increased risk of breast cancer.
Microsatellite instability and high tumor mutational burden detected by next generation sequencing are concordant with loss of mismatch repair proteins by immunohistochemistry.
Yang RK, Alvarez H, Lucas AS … +10 more , Roy-Chowdhuri S, Rashid A, Chen H, Ballester LY, Sweeney K, Routbort MJ, Patel KP, Luthra R, Medeiros LJ, Toruner GA
Cancer Genet · 2025 Jan · PMID 39700818 · Publisher ↗
Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mism...
Impairment of DNA mismatch repair function in neoplasms can be assessed by DNA-based methods to assess for high microsatellite instability (MSI-High) or immunohistochemical (IHC) analysis to assess for deficiency of mismatch repair proteins (dMMR). Neoplasms with mismatch repair deficiency often have high tumor mutational burden (TMB-High). MSI-High, dMMR, and TMB-High are all histology agnostic biomarkers for potential therapy using immune checkpoint inhibitors (ICI). In this single center, retrospective study, our primary aim was to assess if NGS-based positive TMB/MSI findings are concordant with patient matched concurrent MMR IHC studies. In addition, we determined if positive TMB/MSI findings are attributable to genetic/epigenetic alterations of MMR genes. Finally, we explored potential associations between IHC, TMB and MSI findings and specific tumor types We screened 4,258 patients in our database who had tumor-normal-testing with our institutional high-throughput NGS-based CLIA assay between Apr 1, 2021-August 31, 2022 for TMB and MSI. We identified 65 patients who had neoplasms with documented TMB-High/MSI-High (n = 59) or TMB-High/MSI-Undetermined (n = 6) results as well as concurrent IHC results for MMR proteins [colorectal (n = 25), endometrial (n = 28), prostatic (n = 7), urothelial (n = 3), other (n = 5)]. The concordance between positive NGS TMB/MSI and MMR results was 98 %. Genetic/epigenetic alterations of MMR genes were documented in 78 % of the neoplasms. IHC studies for dMMR proteins revealed loss of MLH1/PMS2 (n = 33), MSH2/MSH6 (n = 14), MLH1/MSH2/PMS2 (n = 1), MLH1 (n = 1), MSH2 (n = 2), MSH6 (n = 6) and PMS2 (n = 6). All six prostatic neoplasms with dMMR had loss of MSH2/MSH6 (p < 0.0001). We conclude that neoplasms with positive results for TMB/MSI are highly concordant with positive dMMR results. Genetic/epigenetic alterations in the MMR genes are an underlying reason for most positive findings. The association of MSH2/MSH6 loss with prostatic neoplasms is of in-terest, but sample size is limited, and further studies are warranted to address this association.
Genetic profile in primary tumor tissue of advanced lung adenocarcinoma patients with adrenal metastasis.
Pan H, Zhang H, Zhang Y … +7 more , Chen X, Liu Z, Wu Y, Bai N, Shi Y, Zhao M, Zhu L
Cancer Genet · 2025 Jan · PMID 39673828 · Publisher ↗
The aim of this study was to examine the genomic characteristics and explore the molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. 57 patients diagnosed with lung adenocarcinoma (LUAD) and adrena...
The aim of this study was to examine the genomic characteristics and explore the molecular mechanisms underlying adrenal metastases in lung adenocarcinoma. 57 patients diagnosed with lung adenocarcinoma (LUAD) and adrenal metastases (AM) were enrolled, alongside 33 controls diagnosed with non-adrenal metastases (non-AM) at the time of diagnosis. The primary lung cancer tissue sample were analyzed using next-generation sequencing. The molecular and clinical features were correlated with clinical outcomes. TP53, EGFR and KRAS were the most frequently mutated gene in both groups. EGFR mutations, especially rare variants (G724A, L747P, Q701 L, G719C, V769 L and S768I), exhibited significant enrichment in the non-AM group (P<0.001). An elevated age-related signature in the group of patients with AM, whereas the non-AM group exhibited a higher BRCA signature. Potential prognostic biomarkers such as KEAP1, LRP1B, NOTCH1 and RET mutations were detected in the non-AM group, while ALK mutations in the AM group correlated with shorter overall survival (P<0.001). KRAS mutations in the early synchronous adrenal metastases group were also associated with shorter OS (P<0.001). The analysis of 425 tumor genes in 29 patients with adrenal metastases showed significant enrichment in pathways associated with invasion and metastasis, including TNF signaling pathway and TGF-β signaling pathway. Patients without EGFR mutations in LUAD need to be more concerned about adrenal metastases. Meanwhile, patients with adrenal metastases harboring ALK or KRAS mutations have a poor prognosis and require more aggressive treatment. The TNF and TGF-β pathways might be associated with adrenal metastasis.
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