[{"accession":"PRJDB10974","date":"2021/07/29","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Establishment organoids (cell lines) and Patient-derived xenograft models of salivary gland cancer, such as adenoid cystic carcinoma, salivary duct carcinoma, myoepithelial carcinoma, mucoepidermoid carcinoma.","title":"Establishment of salivary gland cancer organoids and Patient-derived xenograft models","type":"Transcriptome or Gene expression","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJDB10974"},{"accession":"PRJNA110983","date":"2008/10/01","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Salivary gland myoepithelial tumors are relatively uncommon tumors with an unpredictable clinical course. More knowledge about their genetic profiles is necessary to identify novel predictors of disease. In this study, we subjected 27 primary tumors (15 myoepitheliomas and 12 myoepithelial carcinomas) to genome-wide microarray-based comparative genomic hybridization (array CGH). We set out to delineate known chromosomal aberrations in more detail and to unravel chromosomal differences between benign myoepitheliomas and myoepithelial carcinomas. Patterns of DNA copy number aberrations were analyzed by unsupervised hierarchical cluster analysis. Both benign and malignant tumors revealed a limited amount of chromosomal alterations (median of 5 and 7.5 respectively). In both tumor groups, high frequency gains (≥20%) were found mainly at loci of growth factors and growth factor receptors (e.g. PDGF, FGF(R)s, and EGFR). In myoepitheliomas, high frequency losses (≥20%) were detected at regions of proto-cadherins. Cluster analysis of the array CGH data identified three clusters. Differential copy numbers on chromosome arm 8q and chromosome 17 set the clusters apart. Cluster 1 contained a mixture of the two phenotypes (n=10), cluster 2 included mostly benign tumors (n=10), and cluster 3 only contained carcinomas (n=7). Supervised analysis between malignant and benign tumors revealed a 36 Mbp-region at 8q being more frequently gained in malignant tumors (p=0.007, FDR=0.05). This is the first study investigating genomic differences between benign and malignant myoepithelial tumors of the salivary glands at a genomic level. Both unsupervised and supervised analysis of the genomic profiles revealed chromosome arm 8q to be involved in the malignant phenotype of salivary gland myoepitheliomas. Overall design: FFPE material was used throughout the study. 15 primary myoepitheliomas and 12 malignant myoepitheliomas were analyzed on two different BAC platforms, both with 1 Mb spatial resolution. To investigate amplified regions in more detail, a 44k oligo platform was employed on a malignant myoepithelioma. After extraction, DNA quality was assessed by isothermal amplification (Buffart et al., 2007). Only DNAs which scored as excellent, good, or intermediate were used for array CGH analysis. Genomic DNA (600 ng) from both the test and reference sample was labeled and hybridizations were essentially performed according to Snijders et al. (Snijders et al., 2001) without the prehybridization step. Spot analysis and quality control for the BAC arrays were fully automated using Bluefuse 3.4 edition software (BlueGnome, Cambridge, UK). Spots with Quality flag <1 or Confidence value <0.3 were excluded. Log2ratios (tumor signal divided by normal reference signal) of spots that were not excluded after quality flagging and mapping were normalized to their block median value. For the array analysis, BAC clones were positioned along the genome using the March 2006 freeze of the UCSC database. For each clone the average of the triplicate spots was calculated and ratios were normalized by subtraction of the median value of all BAC clones on chromosomes 1-22. The sex chromosomes were discarded from the analysis, since all tumor samples were hybridized to reference DNA of the opposite gender.","title":"Chromosomal aberrations in benign and malignant salivary gland myoepitheliomas","type":"Variation","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA110983"},{"accession":"PRJNA1518243","date":"2026/08/25","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Clear cell odontogenic carcinoma (CCOC) and hyalinizing clear cell carcinoma (HCCC) are rare head-and-neck malignancies with recurrent EWSR1::CREB family fusions that show overlapping morphology and immunophenotype, but whose molecular relationship to each other and to relevant differential diagnoses has remained poorly defined due to tissue rarity. No standardized systemic therapy exists for either tumor.  We performed spatial transcriptomic profiling (NanoString GeoMx Whole Transcriptome Atlas), multiplex immunofluorescence, and RNA in situ hybridization on 80 FFPE tumor samples spanning CCOC, HCCC, clear cell sarcoma, and six additional head-and-neck comparator tumors (squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, myoepithelial carcinoma, Ewing sarcoma, and prostate carcinoma as an outgroup).  CCOC and HCCC showed highly concordant, overlapping global transcriptomic profiles and converged on a shared epithelial-secretory program, with strong enrichment of IGF2 and candidate therapeutic targets including TACSTD2 (TROP2), FGFR2, FOLR1, KDR, MSLN, and MUC1. Clear cell sarcoma, despite sharing the same fusion family, remained transcriptomically distinct. Immune profiling revealed a cold tumor microenvironment in CCOC/HCCC, with low B2M and HLA class I expression, sparse lymphoid infiltration, and minimal PD-L1 expression, consistent with impaired antigen presentation.  These findings indicate that CCOC and HCCC share a common molecular identity distinct from other relevant head-and-neck tumors, particularly myoepithelial carcinoma and squamous cell carcinoma, providing a framework to improve diagnostic classification and prioritize therapeutic targets for these exceptionally rare cancers.","title":"Comparative transcriptomic and immune profiling identifies a shared molecular identity in clear cell odontogenic carcinoma and hyalinizing clear cell carcinoma [1]","type":"Other","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1518243"},{"accession":"PRJNA1518823","date":"2026/08/26","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Clear cell odontogenic carcinoma (CCOC) and hyalinizing clear cell carcinoma (HCCC) are rare head-and-neck malignancies with recurrent EWSR1::CREB family fusions that show overlapping morphology and immunophenotype, but whose molecular relationship to each other and to relevant differential diagnoses has remained poorly defined due to tissue rarity. No standardized systemic therapy exists for either tumor.  We performed spatial transcriptomic profiling (NanoString GeoMx Whole Transcriptome Atlas), multiplex immunofluorescence, and RNA in situ hybridization on 80 FFPE tumor samples spanning CCOC, HCCC, clear cell sarcoma, and six additional head-and-neck comparator tumors (squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, myoepithelial carcinoma, Ewing sarcoma, and prostate carcinoma as an outgroup).  CCOC and HCCC showed highly concordant, overlapping global transcriptomic profiles and converged on a shared epithelial-secretory program, with strong enrichment of IGF2 and candidate therapeutic targets including TACSTD2 (TROP2), FGFR2, FOLR1, KDR, MSLN, and MUC1. Clear cell sarcoma, despite sharing the same fusion family, remained transcriptomically distinct. Immune profiling revealed a cold tumor microenvironment in CCOC/HCCC, with low B2M and HLA class I expression, sparse lymphoid infiltration, and minimal PD-L1 expression, consistent with impaired antigen presentation.  These findings indicate that CCOC and HCCC share a common molecular identity distinct from other relevant head-and-neck tumors, particularly myoepithelial carcinoma and squamous cell carcinoma, providing a framework to improve diagnostic classification and prioritize therapeutic targets for these exceptionally rare cancers.","title":"Comparative transcriptomic and immune profiling identifies a shared molecular identity in clear cell odontogenic carcinoma and hyalinizing clear cell carcinoma  [2]","type":"Other","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1518823"},{"accession":"PRJNA390610","date":"2017/06/15","names_disease":true,"organism":"","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Myoepithelial carcinoma (MECA) is an aggressive type of salivary gland cancer with largely unknown molecular features. There are no active systemic therapies currently available, and recurrent or metastatic disease is generally incurable. MECA may arise de novo or result from oncogenic transformation of a pre-existing pleomorphic adenoma (MECA ex-PA). In this study, we comprehensively analyzed the spectrum of molecular alterations in MECA using whole exome sequencing, RNA sequencing and array comparative genomic hybridization. Our analyses revealed a low mutational load (0.5/MB), but a high prevalence of fusion genes (28/40 tumors; 70%). Many tumors (21/40; 53%) harbored translocations involving the PLAG1 oncogene, which were associated with PLAG1 overexpression. The novel TGFBR3-PLAG1 fusion was found in 6 (15%) cases, and was specific for MECA de novo tumors or the malignant component of MECA ex-PA. This fusion was associated with overexpression of both TGFBR3 and PLAG1, was not found in 723 other salivary gland tumors, and exhibited a tumorigenic phenotype in vitro. The FGFR1-PLAG1 fusion was enriched 15-fold in MECA ex-PA compared to PA. We discovered other novel PLAG1 translocations, including ND4-PLAG1, which is to our knowledge the first reported oncogenic fusion between mitochondrial and nuclear DNA. One tumor harbored a novel MSN-ALK fusion, which was tumorigenic in vitro, and targetable with ALK inhibitors. Furthermore, we found that copy number alterations (CNAs) were more common in MECA ex-PAs than in MECA de novo tumors, and a high number of CNAs was associated with poor survival. We found that several fusion genes were associated with potentially immunogenic neoepitopes, suggesting that neoantigen-based therapies may have value in MECA despite low mutational load. Together, our findings nominate PLAG1 and ALK-targeted therapies for further investigation in MECA, and provide a framework for the next steps of diagnostic and therapeutic research in this lethal cancer.","title":"Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions","type":"Raw sequence reads","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA390610"},{"accession":"GSE12951","date":"2008/10/01","names_disease":true,"organism":"Homo sapiens","pubmed_ids":["19009612"],"samples":28,"source":"GEO","summary":"Salivary gland myoepithelial tumors are relatively uncommon tumors with an unpredictable clinical course. More knowledge about their genetic profiles is necessary to identify novel predictors of disease. In this study, we subjected 27 primary tumors (15 myoepitheliomas and 12 myoepithelial carcinomas) to genome-wide microarray-based comparative genomic hybridization (array CGH). We set out to delineate known chromosomal aberrations in more detail and to unravel chromosomal differences between benign myoepitheliomas and myoepithelial carcinomas. Patterns of DNA copy number aberrations were analyzed by unsupervised hierarchical cluster analysis. Both benign and malignant tumors revealed a limited amount of chromosomal alterations (median of 5 and 7.5 respectively). In both tumor groups, high frequency gains (≥20%) were found mainly at loci of growth factors and growth factor receptors (e.g. PDGF, FGF(R)s, and EGFR). In myoepitheliomas, high frequency losses (≥20%) were detected at regions of proto-cadherins. Cluster analysis of the array CGH data identified three clusters. Differential copy numbers on chromosome arm 8q and chromosome 17 set the clusters apart. Cluster 1 contained a mixture of the two phenotypes (n=10), cluster 2 included mostly benign tumors (n=10), and cluster 3 only contained carcinomas (n=7). Supervised analysis between malignant and benign tumors revealed a 36 Mbp-region at 8q being more frequently gained in malignant tumors (p=0.007, FDR=0.05). This is the first study investigating genomic differences between benign and malignant myoepithelial tumors of the salivary glands at a genomic level. Both unsupervised and supervised analysis of the genomic profiles revealed chromosome arm 8q to be involved in the malignant phenotype of salivary gland myoepitheliomas. ","title":"Chromosomal aberrations in benign and malignant salivary gland myoepitheliomas","type":"Genome variation profiling by genome tiling array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12951"},{"accession":"GSE345045","date":"2026/08/26","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":1000,"source":"GEO","summary":"Clear cell odontogenic carcinoma (CCOC) and hyalinizing clear cell carcinoma (HCCC) are rare head-and-neck malignancies with recurrent EWSR1::CREB family fusions that show overlapping morphology and immunophenotype, but whose molecular relationship to each other and to relevant differential diagnoses has remained poorly defined due to tissue rarity. No standardized systemic therapy exists for either tumor.  We performed spatial transcriptomic profiling (NanoString GeoMx Whole Transcriptome Atlas), multiplex immunofluorescence, and RNA in situ hybridization on 80 FFPE tumor samples spanning CCOC, HCCC, clear cell sarcoma, and six additional head-and-neck comparator tumors (squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, myoepithelial carcinoma, Ewing sarcoma, and prostate carcinoma as an outgroup).  CCOC and HCCC showed highly concordant, overlapping global transcriptomic profiles and converged on a shared epithelial-secretory program, with strong enrichment of IGF2 and candidate therapeutic targets including TACSTD2 (TROP2), FGFR2, FOLR1, KDR, MSLN, and MUC1. Clear cell sarcoma, despite sharing the same fusion family, remained transcriptomically distinct. Immune profiling revealed a cold tumor microenvironment in CCOC/HCCC, with low B2M and HLA class I expression, sparse lymphoid infiltration, and minimal PD-L1 expression, consistent with impaired antigen presentation.  These findings indicate that CCOC and HCCC share a common molecular identity distinct from other relevant head-and-neck tumors, particularly myoepithelial carcinoma and squamous cell carcinoma, providing a framework to improve diagnostic classification and prioritize therapeutic targets for these exceptionally rare cancers.","title":"Comparative transcriptomic and immune profiling identifies a shared molecular identity in clear cell odontogenic carcinoma and hyalinizing clear cell carcinoma [1]","type":"Other","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345045"},{"accession":"GSE345112","date":"2026/08/26","names_disease":true,"organism":"Homo sapiens","pubmed_ids":[],"samples":810,"source":"GEO","summary":"Clear cell odontogenic carcinoma (CCOC) and hyalinizing clear cell carcinoma (HCCC) are rare head-and-neck malignancies with recurrent EWSR1::CREB family fusions that show overlapping morphology and immunophenotype, but whose molecular relationship to each other and to relevant differential diagnoses has remained poorly defined due to tissue rarity. No standardized systemic therapy exists for either tumor.  We performed spatial transcriptomic profiling (NanoString GeoMx Whole Transcriptome Atlas), multiplex immunofluorescence, and RNA in situ hybridization on 80 FFPE tumor samples spanning CCOC, HCCC, clear cell sarcoma, and six additional head-and-neck comparator tumors (squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, myoepithelial carcinoma, Ewing sarcoma, and prostate carcinoma as an outgroup).  CCOC and HCCC showed highly concordant, overlapping global transcriptomic profiles and converged on a shared epithelial-secretory program, with strong enrichment of IGF2 and candidate therapeutic targets including TACSTD2 (TROP2), FGFR2, FOLR1, KDR, MSLN, and MUC1. Clear cell sarcoma, despite sharing the same fusion family, remained transcriptomically distinct. Immune profiling revealed a cold tumor microenvironment in CCOC/HCCC, with low B2M and HLA class I expression, sparse lymphoid infiltration, and minimal PD-L1 expression, consistent with impaired antigen presentation.  These findings indicate that CCOC and HCCC share a common molecular identity distinct from other relevant head-and-neck tumors, particularly myoepithelial carcinoma and squamous cell carcinoma, providing a framework to improve diagnostic classification and prioritize therapeutic targets for these exceptionally rare cancers.","title":"Comparative transcriptomic and immune profiling identifies a shared molecular identity in clear cell odontogenic carcinoma and hyalinizing clear cell carcinoma  [2]","type":"Other","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345112"},{"accession":"PRJNA108463","date":"2008/07/14","names_disease":false,"organism":"Homo sapiens","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Myoepithelioma, mixed tumor and parachordoma are rare soft tissue tumors thought to represent different morphologic variants of the same family of tumors, hereafter referred to as MMP tumors. The genetic basis of these neoplasms is poorly investigated. However, they morphologically resemble mixed tumor of the salivary glands (a.k.a. pleomorphic adenoma). This is the first study characterizing whole genome DNA copy number changes in MMP tumors and the genomic imbalances detected in four MMP tumors and one pleomorphic adenoma were diverse. The only recurrent aberration of known importance for tumor development was homo- and heterozygous deletions of the region in 9p21-22 which harbors the CDKN2A and CDKN2B genes. Defined by the deletion in case 3, the region 1.27-4.82 Mb on chromosome 19 was heterozygously lost in all cases, including the pleomorphic adenoma. A complex pattern of aberrations was seen in the primary tumor of case 2 with amplifications, interrupted by normal copy numbers and losses, of regions on chromosomes 6, 9, and 13. Keywords: comparative genomic hybridization, soft tissue myoepithelioma, mixed tumor, parachordoma, pleomorphic adenoma Overall design: Cases 1-3 and 5-6 were analyzed using 32k array CGH and male genomic DNA (Promega) was used as reference.","title":"Heterogeneous genetic profiles in soft tissue myoepitheliomas","type":"Variation","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA108463"},{"accession":"PRJNA243292","date":"2014/03/31","names_disease":false,"organism":"Mus musculus","pubmed_ids":[],"samples":null,"source":"BioProject","summary":"Previously we have demonstrated that inactivation of retinoic acid receptor beta (Rarb) in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis although Rarb has been reported as a tumor suppressor before. In the current study, we further confirmed that ablation of Rarb has a very similar impact on Wnt1-induced mammary gland tumorigenesis as those on ErbB2-induced mammary gland tumorigenesis. Nevertheless, the mechanisms by which Rarb confers its effects on tumor progression is quite different although both involving in tumor microenvironment (TME) remodeling. In the Wnt1 tumors, ectopic wnt1 produced by malignant luminal cells activates nearby stromal cells by a paracrine manner. In return, the stromal cells secreted IGF1 to regulate the growth of tumor cells. There is a need of Rarb expression in this interaction. Deletion of Rarb inhibits both wnt1/β-catenin signaling and IGF1/Akt axis in the myoepithelial tumor cells which results in the suppression of epithelial-mesenchymal transition (EMT) in these tumors. Since wnt1 tumors resemble basal-like breast cancer with a poor clinical prognosis in which EMT is one of the most important way for tumor cells to survive against standard treatment and to go to metastasis, we propose that (1) the stromal gene expression signature of Rarb ablation in wnt1 tumors could have some clinical value in predicting the breast cancer outcome; and (2) Rarb antagonist might be a potential therapeutic strategy in EMT-driven aggressive cancers such as basal-like breast cancer. Overall design: Laser capture microdissection (LCM) was performed to separate the mammary tumor samples into epithelial cell compartment and stromal cell compartment. Transcriptional profiling of the two compartments were investigated by microarray analysis.","title":"wnt1-induced mammary tumor from Rarb KO mice vs. those from Rarb wt (control)","type":"Transcriptome or Gene expression","url":"https://www.ncbi.nlm.nih.gov/bioproject/PRJNA243292"},{"accession":"GSE10266","date":"2008/07/14","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["18604193"],"samples":5,"source":"GEO","summary":"Myoepithelioma, mixed tumor and parachordoma are rare soft tissue tumors thought to represent different morphologic variants of the same family of tumors, hereafter referred to as MMP tumors. The genetic basis of these neoplasms is poorly investigated. However, they morphologically resemble mixed tumor of the salivary glands (a.k.a. pleomorphic adenoma). This is the first study characterizing whole genome DNA copy number changes in MMP tumors and the genomic imbalances detected in four MMP tumors and one pleomorphic adenoma were diverse. The only recurrent aberration of known importance for tumor development was homo- and heterozygous deletions of the region in 9p21-22 which harbors the CDKN2A and CDKN2B genes. Defined by the deletion in case 3, the region 1.27-4.82 Mb on chromosome 19 was heterozygously lost in all cases, including the pleomorphic adenoma. A complex pattern of aberrations was seen in the primary tumor of case 2 with amplifications, interrupted by normal copy numbers and losses, of regions on chromosomes 6, 9, and 13. Keywords: comparative genomic hybridization, soft tissue myoepithelioma, mixed tumor, parachordoma, pleomorphic adenoma","title":"Heterogeneous genetic profiles in soft tissue myoepitheliomas","type":"Genome variation profiling by genome tiling array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10266"},{"accession":"GSE119810","date":"2019/07/22","names_disease":false,"organism":"Canis lupus familiaris","pubmed_ids":["32680987"],"samples":222,"source":"GEO","summary":"Canine mammary gland tumors (CMTs) have been suggested as promising cancer models to human breast cancer due to their many biological and clinical similarities. Here, we collected 222 samples consist of 158 tumor samples and 64 matched normal samples of CMTs. Fresh tissue samples were transferred in to RNAlater, and refrigerated overnight at 4°C and then stored at -80°C. Total RNA was extracted from tissues using RNeasy mini kit. We aligned RNA-Seq raw data from 222 samples to canine reference genome CanFam3.1 using Tophat. We assembled transcript and calculated FPKM values using Cufflinks. All tumor samples were evaluated by histopathological characteristics including histopathological subtype, grade, and lymphatic invasion, and annotated with corresponding sequencing data. The histopathological classification and the histological grading system of CMTs were adopted from those of human breast cancer. In addition, immunohistochemical evaluation was performed in samples for estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status.  DISCLAIMER: Using this dataset became freely available on Jul 22, 2019. On the other hand, we are now preparing a key paper about comparative analysis of canine and human breast cancer based on this dataset. If you plan to submit a similar paper using this dataset before the main paper is published, please feel free to contact the submitter ([address removed]) to coordinate submission.","title":"RNA-seq data of canine mammary tumors and normal samples","type":"Expression profiling by high throughput sequencing","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE119810"},{"accession":"GSE243075","date":"2024/08/31","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["39332710"],"samples":363,"source":"GEO","summary":"Tumors of the major and minor salivary gland encompass a diverse spectrum of diagnostically challenging neoplasms. Recent studies have identified several gene fusions and somatic mutations that are specific or highly enriched in certain salivary gland tumor entities and can assist histopathological diagnosis. Still, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that can be used to classify diagnostically challenging cases.","title":"DNA methylation profiling of salivary gland tumors","type":"Methylation profiling by genome tiling array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243075"},{"accession":"GSE276299","date":"2024/10/10","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["39358389"],"samples":950,"source":"GEO","summary":"As part of the advancement in therapeutic decision-making for brain tumor patients at St. Jude Children’s Research Hospital (SJCRH), we developed three robust classifiers, a deep learning neural network (NN), k-nearest neighbor (kNN), and random forest (RF), trained on a reference series DNA-methylation profiles to classify central nervous system (CNS) tumor types. The models’ performance was rigorously validated against 2,054 samples from two independent cohorts. In addition to classic metrics of model performance, we compared the robustness of the three models to reduced tumor purity, a critical consideration in the clinical utility of such classifiers. Our findings revealed that the NN model exhibited the highest accuracy and maintained a balance between precision and recall. The NN model was the most resistant to drops in performance associated with a reduction in tumor purity, showing good performance until the purity fell below 50%. Through rigorous validation, our study emphasizes the potential of DNA-methylation-based deep learning methods to improve precision medicine for brain tumor classification in the clinical setting.","title":"Comparison of DNA Methylation Based Classification Models for Precision Diagnostics of Central Nervous System Tumors","type":"Methylation profiling by genome tiling array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE276299"},{"accession":"GSE279837","date":"2025/11/30","names_disease":false,"organism":"Homo sapiens","pubmed_ids":[],"samples":30,"source":"GEO","summary":"Soft tissue myoepithelial tumors (METs) are diagnostically challenging tumors that require careful histologic and immunohistochemical characterization for accurate classification. Nearly half of METs show recurrent EWSR1 or FUS gene rearrangements with a diverse set of fusion partners. The diversity of fusion partners and lack of known driver abnormalities in many cases raise the question of whether METs represent a uniformly distinct tumor entity. To address this question, we performed careful histopathologic and molecular analysis, including DNA methylation profiling (DNA-MP) and fusion testing, on a cohort of 30 institutionally diagnosed METs from 29 patients. On histologic and immunophenotypic evaluation, 22 of 30 tumors diagnosed as MET fulfilled strict histologic and immunophenotypic criteria. Among those failing to meet criteria, most were reclassified as another tumor entity by DNA-MP. 7 tumors meeting criteria grouped with another sarcoma reference type by DNA-MP, with confirmation of the characteristic driver abnormality of that tumor in selected cases. The remaining tumors histologically “consistent” with METs (n = 15) formed a distinct epigenetic cluster, independent of other reference entities. Recurrent gene fusions were identified in 11 of 15 tumors in this epigenetically distinct group, including EWSR1::KLF15 (n= 4), EWSR1::PBX3 (n= 2), and EWSR1::POU5F1 (n = 1)  rearrangements. Clinicopathologic correlation suggests that EWSR1::KLF15 tumors are enriched in pediatric patients with aggressive histology. Our work shows that not all tumors meeting the strict morphologic and immunohistochemical diagnostic criteria for METs fall within one distinct epigenetic tumor group. Furthermore, DNA-MP provides a useful adjunct to other molecular testing to help distinguish METs from histologic mimics","title":"Reappraisal of Soft Tissue Myoepithelial Tumors by DNA Methylation Profiling Reveals an Epigenetically Distinct Group of Mostly Fusion-Driven Neoplasms","type":"Methylation profiling by array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE279837"},{"accession":"GSE293967","date":"2025/06/11","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["40311763"],"samples":66,"source":"GEO","summary":"Salivary gland tumors (SGTs) are a rare and heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The most common SGT subtype, pleomorphic adenoma (PA), can undergo malignant transformation into carcinoma ex pleomorphic adenoma (CXPA). Carcinomatous transformation from PA to CXPA is a highly progressive and multi-step process. Distinguishing a PA with some atypia from a low-grade intracapsular or minimally invasive CXPA is primarily subjective as no mitotic count thresholds exist to help pathologists distinguish between them in difficult cases.  In this prospective study, we collected 140 cases encompassing both PA and CXPA to study their molecular signatures. The primary objective was to investigate the use of DNA methylation profiling as a potential molecular tool for differentiating between these two entities. Methylation analysis was performed on 33 PA cases and 33 CXPA cases. We were able to demonstrate that based on their methylation profiles, PA and CXPA could be classified into three distinct clusters that we called benign, intermediate, and malignant. We also revealed that the presence of TP53, HRAS, PTEN and/or TERT pathogenic mutations were exclusively present in CXPA cases; and that chromosomal alteration on chromosomes 5 and 8 are potentially associated with malignant transformation.   In conclusion, our study provides a comprehensive molecular framework for PA and CXPA.  The presence of a pathogenic mutation in TP53, HRAS, PTEN, or pTERT or HER2 amplification could be integrated into a molecular diagnosis of CXPA for tumors within the PA CXPA spectrum. In the future, we aim to improve our methylomic classification to make it a precision medicine diagnostic tool for the treatment management of tumors within the PA-CXPA spectrum.","title":"Malignant Transformation in Pleomorphic Adenoma:   The impact of DNA methylation profiling and Pathogenic Mutations","type":"Methylation profiling by array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293967"},{"accession":"GSE294016","date":"2025/04/14","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["40506428"],"samples":95,"source":"GEO","summary":"Salivary gland cancers are rare, diverse malignancies characterized by poor response to immunotherapy. The tumor immune environment in these cancers remains poorly understood. To address this, we perform an integrative analysis of the tumor immune microenvironment in a large cohort of advanced salivary gland cancer samples. Most tumors exhibit low immune activity with limited immune cell infiltration. Inflammation is linked to higher tumor mutational burden in non-adenoid cystic carcinoma histologies. Subtype specific expression of immune checkpoints is identified with prominent expression of VTCN1 in luminal-like cells within adenoid cystic carcinoma. Macrophages with immunosuppressive properties dominate the immune microenvironment across subtypes. Responses to immunotherapy are limited and associated with a higher ratio of T-cells relative to macrophages in individual cases, warranting further investigation. Here, we show an immunosuppressive environment in salivary gland cancers and identify subtype-specific immune vulnerabilities that could inform tailored therapeutic strategies.","title":"A macrophage-predominant, immunosuppressive immune microenvironment and subtype-specific therapeutic vulnerabilities in advanced salivary gland cancer [bulk RNA-seq]","type":"Expression profiling by high throughput sequencing","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294016"},{"accession":"GSE300102","date":"2025/11/09","names_disease":false,"organism":"Homo sapiens","pubmed_ids":["41342886"],"samples":52,"source":"GEO","summary":"DNA methylation profiling from a multi-institutional cohort of 52 fusion-positive MET cases were analyzed. Pooled clinicopathological and outcome analysis with new and published cases (total 185 and 69 cases, respectively) was performed. The MET subgroups, EWSR1::KLF15, EWSR1/FUS::KLF17, EWSR1::PBX1, EWSR1::PBX3, EWSR1/FUS::POU5F1, SS18::POU5F1, and EWSR1::ZNF444, showed significant heterogeneity in age group, site, and histology. DNA methylation analysis revealed that fusion-positive MET were epigenetically related to each other and EWSR1/FUS::NFATC2 sarcomas, but entirely distinct from the epigenetically-related PLAG1-rearranged and salivary gland MET.","title":"FET-Rearranged Soft Tissue Myoepithelial Tumors Span a Broad Clinicopathologic and Molecular Spectrum that is Epigenetically Distinct from Cutaneous and Head and Neck Myoepithelial Tumors","type":"Methylation profiling by genome tiling array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300102"},{"accession":"GSE56391","date":"2014/10/23","names_disease":false,"organism":"Mus musculus","pubmed_ids":["25422594"],"samples":12,"source":"GEO","summary":"Previously we have demonstrated that inactivation of retinoic acid receptor beta (Rarb) in the mouse results in a protective effect against ErbB2-induced mammary gland tumorigenesis although Rarb has been reported as a tumor suppressor before. In the current study, we further confirmed that ablation of Rarb has a very similar impact on Wnt1-induced mammary gland tumorigenesis as those on ErbB2-induced mammary gland tumorigenesis. Nevertheless, the mechanisms by which Rarb confers its effects on tumor progression is quite different although both involving in tumor microenvironment (TME) remodeling. In the Wnt1 tumors, ectopic wnt1 produced by malignant luminal cells activates nearby stromal cells by a paracrine manner. In return, the stromal cells secreted IGF1 to regulate the growth of tumor cells. There is a need of Rarb expression in this interaction. Deletion of Rarb inhibits both wnt1/β-catenin signaling and IGF1/Akt axis in the myoepithelial tumor cells which results in the suppression of epithelial-mesenchymal transition (EMT) in these tumors. Since wnt1 tumors resemble basal-like breast cancer with a poor clinical prognosis in which EMT is one of the most important way for tumor cells to survive against standard treatment and to go to metastasis, we propose that (1) the stromal gene expression signature of Rarb ablation in wnt1 tumors could have some clinical value in predicting the breast cancer outcome; and (2) Rarb antagonist might be a potential therapeutic strategy in EMT-driven aggressive cancers such as basal-like breast cancer.","title":"wnt1-induced mammary tumor from Rarb KO mice vs. those from Rarb wt (control)","type":"Expression profiling by array","url":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56391"}]