Project description:Thymic epithelial tumors are a group of neoplasms with heterogeneous histological features and clinical behavior. The identification of markers useful to predict patient prognosis and molecular targets for therapies is limited by a very little understanding of the biology of these neoplasms. We evaluated the copy number (CN) aberrations of genes involved in normal thymus development in thymic epithelial tumors, following the intriguing idea that the ectopic deregulation of genes relevant for proliferation and differentiation of embryonic cells, can contribute to tumor growth. Frequent CN losses of FOXC1 were observed in more aggressive tumors and correlated with a reduced protein expression; tumors negative for FOXC1 expression were associated with a shorter time to progression. In addition, FOXC1 showed tumor suppressor activity in in-vitro models. Our data indicate that FOXC1 loss can identify a group of thymic epithelial tumors with poor prognosis, possibly because its tumor suppressor properties. Two color array CGH of a series of 59 thymic epithelial tumors plus evaluation of 2 thymic carcinoma cell lines and one thymoma B1 cell line.
Project description:Thymic epithelial tumors are a group of neoplasms with heterogeneous histological features and clinical behavior. The identification of markers useful to predict patient prognosis and molecular targets for therapies is limited by a very little understanding of the biology of these neoplasms. We evaluated the copy number (CN) aberrations of genes involved in normal thymus development in thymic epithelial tumors, following the intriguing idea that the ectopic deregulation of genes relevant for proliferation and differentiation of embryonic cells, can contribute to tumor growth. Frequent CN losses of FOXC1 were observed in more aggressive tumors and correlated with a reduced protein expression; tumors negative for FOXC1 expression were associated with a shorter time to progression. In addition, FOXC1 showed tumor suppressor activity in in-vitro models. Our data indicate that FOXC1 loss can identify a group of thymic epithelial tumors with poor prognosis, possibly because its tumor suppressor properties.
Project description:Within a project aim to define the genomic aberration of thymic epithelial tumors, we performed array CGH in 65 thymic epithelial tumors. Tumor samples were collected during surgery or by image-guided biopsies and immediately frozen. Section from frozen material were cut and stained with Haematoxylin and Eosin. A pathologist reviewed the slides and selected only cases with >80% of cancer cells. Copy number aberrations of a series of 65 thymic epithelial tumors were evaluated using array CGH. Differences in copy number aberrations between different histotypes were evaluated. Significant regions of CN aberrations were defined using GISTIC algorithms.
Project description:Methylation microarray data (Illumina 850K) of 52 thymic epithelial tumors. 13 patients with thymoma A and B, 32 thymic carcinoma (TC) and 7 neuroendocrine tumors of the thymus (NET).
Project description:Thymoma and thymic carcinoma represent the two most characterized types of Thymic epithelial tumors (TET) which arise from epithelial cell of thymus. According to the different morphological features, lymphocytes and epithelial cells ratio and grade of malignancy, TET are divided in thymoma A, AB, B1, B2, and B3 and thymic carcinoma. We used microarrays to detail the global programme of gene expression distinguishing tumoral and normal thymic tissue, thus identifying networks of correlated mRNAs-lncRNAs.
Project description:Renal tumors with complex morphology require extensive workup for accurate classification. Chromosomal aberrations that define subtypes of renal epithelial neoplasms have been reported. We explored if whole-genome chromosome copy number and loss-of-heterozygosity analysis with single nucleotide polymorphism (SNP) arrays can be used to identify these aberrations. Keywords: Chromosome copy number and LOH analysis with SNP Genotyping Arrays
Project description:Renal tumors with complex morphology require extensive workup for accurate classification. Chromosomal aberrations that define subtypes of renal epithelial neoplasms have been reported. We explored if whole-genome chromosome copy number and loss-of-heterozygosity analysis with single nucleotide polymorphism (SNP) arrays can be used to identify these aberrations in cases where morphology was unable to definitively classify these tumors. Keywords: Chromosome copy number and LOH analysis (virtual karyotyping) with SNP Genotyping Arrays Keywords: Genome variation profiling by SNP array
Project description:We previously identified a recurrent mutation L424H in the transcription factor GTF2I in thymic epithelial tumors. The precise role of the GTF2I mutation in these tumors is unclear. Here we describe the generation and characterization of a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. The Gtf2i mutation impairs development of thymic medulla and maturation of medullary thymic epithelial cells in the young mice and causes tumor formation in the thymus of the aged KI mice. To characterize the molecular features of murine thymomas, we performed digital spatial profiling with GeoMx moue whole transcriptome atlas assay with FFPE thymic tissues of 4 KI and 4 control mice.
