Identification of the lymphangioleiomyomatosis cell and its uterine origin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA560283 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women which causes cystic lung remodeling and progressive respiratory failure. While LAM lesions are known to contain abnormal smooth muscle-like cells which harbor mTOR activating mutations in TSC1 or TSC2, the tissue origins of the mutant “LAM cells” that invade the lung remain unclear. By employing single cell and single nuclear RNA sequencing on explanted LAM lungs, we identified a unique population of cells and associated signature genes and gene networks which were readily distinguished from those of endogenous lung cells. These unique LAMCORE cells shared closest transcriptomic similarity to normal uterus and share transcriptomic features with neural crest, as identified in uterine LAM lesions by single nuclear RNA-seq. Immunofluorescence microscopy demonstrated the expression of LAMCORE cell signature genes within LAM lesions in both lung and uterus. Serum aptamer proteomics and ELISA identified biomarkers consistent with the signature genes expressed and predicted to be secreted by LAMCORE cells. Single cell transcriptomics strongly supports a uterine neural crest origin of LAMCORE cells; providing insights into disease pathogenesis and informing future treatment strategies for LAM.
2020-07-11 | GSE135851 | GEO
Project description:Identification of driver genes in uterine leiomyosarcoma: RNA seq
| PRJEB21003 | ENA
Project description:ObjectiveTo determine the frequency of uterine leiomyomas and hysterectomy in patients with lymphangioleiomyomatosis (LAM), a disease characterized by proliferation of abnormal-appearing smooth muscle-like cells.DesignRetrospective study.SettingNatural history study at the National Institutes of Health.Patient(s)456 patients with sporadic LAM and LAM associated with tuberous sclerosis complex (LAM/TSC).Intervention(s)Review of records and pelvic computed axial tomography scans.Main outcome measure(s)Prevalence of uterine leiomyomas and hysterectomy.Result(s)A total of 174 women had uterine leiomyomas (38%). One hundred eighteen were diagnosed by computed tomographic scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects with sporadic LAM and 25 of 78 with LAM/TSC. Fifty-six patients were found to have uterine fibroids on hysterectomy. The most common indications for hysterectomy were uterine leiomyoma, LAM, and endometriosis.Conclusion(s)Uterine leiomyomas are not more common in LAM than in the general population. However, in LAM, the frequency of hysterectomy is higher because of it having been recommended for treatment of LAM.
| S-EPMC3165169 | biostudies-literature
Project description:Identification of driver genes in uterine leiomyosarcoma: low-coverage WGS
| PRJEB21002 | ENA
Project description:Carcinomas of unknown primary origin constitute 3-5% of all newly diagnosed metastatic cancers, of which the primary source is difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification
2013-12-01 | GSE50891 | GEO
Project description:Carcinomas of unknown primary origin constitute 3-5% of all newly diagnosed metastatic cancers, of which the primary source is difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor, which is why patients with metastases of unknown origin have poor prognosis and short survival. Because microRNA expression is highly tissue specific, the microRNA profile of a metastasis may be used to identify its origin. As a first step to realize this goal, we evaluated the potential of microRNA profiling for identification of the primary tumor of known metastases. 208 formalin-fixed paraffin-embedded samples representing 15 different histologies were profiled on an LNA-enhanced microarray platform, which allows for highly sensitive and specific detection of microRNA. Based on these data, we developed and cross-validated a novel classification algorithm, LASSO (Least Absolute Shrinkage and Selection Operator), which had an overall accuracy of 85%. When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy). Our findings suggest that microRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor, and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors, and eventually, enable tailored therapy. 94 samples
2013-12-01 | E-GEOD-50890 | biostudies-arrayexpress
Project description:Carcinomas of unknown primary origin constitute 3-5% of all newly diagnosed metastatic cancers, of which the primary source is difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification 220 samples
2013-12-01 | E-GEOD-50891 | biostudies-arrayexpress
Project description:Carcinomas of unknown primary origin constitute 3-5% of all newly diagnosed metastatic cancers, of which the primary source is difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor, which is why patients with metastases of unknown origin have poor prognosis and short survival. Because microRNA expression is highly tissue specific, the microRNA profile of a metastasis may be used to identify its origin. As a first step to realize this goal, we evaluated the potential of microRNA profiling for identification of the primary tumor of known metastases. 208 formalin-fixed paraffin-embedded samples representing 15 different histologies were profiled on an LNA-enhanced microarray platform, which allows for highly sensitive and specific detection of microRNA. Based on these data, we developed and cross-validated a novel classification algorithm, LASSO (Least Absolute Shrinkage and Selection Operator), which had an overall accuracy of 85%. When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy). Our findings suggest that microRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor, and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors, and eventually, enable tailored therapy.
2013-12-01 | GSE50890 | GEO
Project description:Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.
2012-08-07 | GSE39920 | GEO
Project description:Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis. Keywords: Human patient sample comparison with cell lines The study is of case/control design with biological replication. Biopsies of nodules from 14 LAM patients (cases) are compared with cultured cell lines (controls) with similar properties.
2008-12-30 | E-GEOD-12027 | biostudies-arrayexpress