Project description:This SuperSeries is composed of the following subset Series: GSE12592: Gene expression analysis of myxoinflammatory fibroblastic sarcoma, and morphologically similar lesions GSE12593: DNA copy number analysis of myxoinflammatory fibroblastic sarcoma, and morphologically similar lesions Refer to individual Series
Project description:Genetic lesions characteristic for RCC subtypes can be identified by virtual karyotyping with SNP microarrays. In this study, we examined whether virtual karyotypes could be used to better classify a cohort of morphologically challenging/unclassified RCC.
Project description:The fibroblast growth factor receptor (FGFR) and canonical Wnt signaling pathways are important regulators of carcinogenesis; however, the interaction between these two pathways in the context of prostate cancer (PCa) has not been fully elucidated. Using novel transgenic mouse models, we describe Wnt-induced synergistic acceleration of FGFR1-driven adenocarcinoma; largely due to pronounced fibroblastic reactive stroma (RS) activation surrounding prostatic intraepithelial neoplasia (PIN) lesions in endogenous and reconstitution assays. Finally, both mouse and human RS are characterized by increases in TGF-β signaling heterogeneity immediately adjacent to PIN lesions; however, heterogeneity is lost during later stages of progression, likely contributing to tissue invasion. These studies confirm the importance of the FGFR1-Wnt-TGF-β signaling axes as driving forces behind reactive stroma and aggressive adenocarcinoma.
Project description:Clear cell sarcoma (CCS) of tendons and aponeuroses is a deadly soft-tissue malignancy resembling melanoma, with a predilection for young adults. EWS-ATF1, the fusion product of a balanced chromosomal translocation between chromosomes 22 and 12, is considered the definitional feature of the tumor. Conditional expression of the EWS-ATF1 human cDNA in the mouse generates CCS-like tumors with 100 percent penetrance. Tumors, developed through varied means of initiating expression of the fusion oncogene, model human CCS morphologically, immunohistochemically, and by genome-wide expression profiling. We also demonstrate that while fusion oncogene expression in later stages of differentiation can transform mesenchymal progenitor cells and generate tumors resembling CCS generally, expression in cells retaining stem cell markers permits the full melanoma-related phenotype. Nielsen et al. ("Molecular characterisation of soft tissue tumours: a gene expression study"; PMID 11965276) used microarray to compare a variety of soft-tissue neoplasms morphologically similar to clear cell sarcoma. In our study, we use their expression data (not previously submitted) in the profiling of our mouse mutant that models clear cell sarcoma.
Project description:Low grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs in association with lobular intraepithelial neoplasia (LIN). The aim of this study was to elucidate chromosomal aberrations in these early neoplastic breast lesions using array comparative genomic hybridization (CGH) analysis. Laser capture microdissection of 12 archival formalin-fixed, paraffin-embedded specimens harbouring both foci of DIN1a as well as LIN was performed. All analyzed cases of DIN1a and LIN showed chromosomal gains and losses. The aberration encountered most often was loss on 16q in 7 DIN1a (70%) and 10 LIN (91%) cases. Regarding changes in chromosome 1, four DIN1a (40%) and 7 LIN (64%) cases showed a gain on 1q. The results of our study show concurrent chromosomal aberrations of 1q gains and 16q losses in several cases with coexisting LIN and low grade flat DIN. These aberrations are known to be common in low grade invasive ductal carcinomas as well as more advanced (conventional) types of low grade DIN (low grade ductal carcinoma in-situ). Our results raise the possibility of similar molecular-genetic pathways in most of the cases with coexisting LIN and low grade flat DIN.
Project description:Clear cell sarcoma (CCS) of tendons and aponeuroses is a deadly soft-tissue malignancy resembling melanoma, with a predilection for young adults. EWS-ATF1, the fusion product of a balanced chromosomal translocation between chromosomes 22 and 12, is considered the definitional feature of the tumor. Conditional expression of the EWS-ATF1 human cDNA in the mouse generates CCS-like tumors with 100 percent penetrance. Tumors, developed through varied means of initiating expression of the fusion oncogene, model human CCS morphologically, immunohistochemically, and by genome-wide expression profiling. We also demonstrate that while fusion oncogene expression in later stages of differentiation can transform mesenchymal progenitor cells and generate tumors resembling CCS generally, expression in cells retaining stem cell markers permits the full melanoma-related phenotype. Nielsen et al. ("Molecular characterisation of soft tissue tumours: a gene expression study"; PMID 11965276) used microarray to compare a variety of soft-tissue neoplasms morphologically similar to clear cell sarcoma. In our study, we use their expression data (not previously submitted) in the profiling of our mouse mutant that models clear cell sarcoma. The mRNA profiles of a variety of soft-tissue neoplasm samples are examined by HEEBO microarrays. Included here are a total of 6 different types of tumors, and 5 of them have at least one biological replicate. The authors of "Molecular characterisation of soft tissue tumours: a gene expression study" (PMID 11965276) performed these microarray experiments, including data processing and normalization. We obtained these expression data, and used them to train a support vector machine, which was later used to characterize our mouse model of clear cell sarcoma (data submitted elsewhere).
Project description:The gain-of-function MUC5B promoter varaint is the dominant risk for IPF development. Herein, we performed laser capture microdissection coupled mass spectrometry to isolate the characteristic histopathological lesions of IPF, the normal-appearing alveoli/small airways, and epithelium overlying fibroblastic foci. The captured samples were subject to mass spectrometry.