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:Thymoma is a rare tumor originating from epithelial cells of thymus. Despite previous studies, molecular trajectories underlying thymic tumorigenesis remain largely unknown. In this study, we conducted an integrated analysis of genomes and transcriptomes from 124 thymomas and 13 thymic carcinomas. Additionally, we incorporated single-cell transcriptomes of normal thymic tissues collected at different developmental stages. The efforts identify two mutually exclusive molecular types of thymomas: GTF2I-mutant (GTF2I-type) and copy number-altered type (CN-type). The GTF2I-type has a stable copy number profile with cellular identities of transcription similar to thymic progenitor cells. In contrast, CN-type tumors show cellular identities resembling differentiated thymic epithelium with distinct metabolic and immune features and activation of oncogene IRS4. Genome-wide timing analyses on CN-type reveal that tumorigenic courses of the two types were partitioned from the early stage in the lifetime. Our findings provide deep insights into the origin and tumorigenic processes of thymic epithelial cells.
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:Background & Aims: The metastatic process is complex and remains a major obstacle in the management of colorectal cancer (CRC). To gain a better insight into the biologic events driving the metastatic process we investigated genomic aberrations in a large cohort of matched CRC primaries and distant metastases from various sites. Methods: In total, 62 primary colorectal cancers, 62 matched normal specimens, and 68 matched metastases (from liver, lung, ovary, omentum, and distant lymph nodes) were analyzed by high resolution array comparative genomic hybridization (array CGH) for DNA copy number changes. Findings were validated using a publicly available dataset consisting of 21 primary tumors and matched liver metastases. Fluorescence in situ hybridization (FISH) was used to confirm some of the DNA copy number changes observed. Results: Overall patterns of DNA copy number aberrations were highly similar between primary tumors and their metastases, confirming clonality. Additional copy number aberrations in metastasis are rare and rather than recurrent they were sporadic for individual patients. The only recurrent differences between primary tumors and their metastases were two chromosomal regions, 6q21 and 8q24.21 encompassing the MYC oncogene, that coamplified in three metastases of two patients (3.2%). FISH analysis confirmed the high level co-amplification in the metastasis, which were not detected in their primary tumors. Conclusions: Primary CRC and their metastases show highly similar patterns of DNA copy number changes, additional copy number aberrations in metastasis are rare and recurrences exceptional. These observations are consistent with the hypothesis that the metastatic potential is predestined early in the development of the primary tumor.