Project description:Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We identified non-overlapping somatic driver mutations in all 26 cases of post-Chernobyl thyroid cancers we studied through candidate gene assays and next generation RNA-sequencing. We found that 22/26 harbored fusion oncogenes arising primarily through intrachromosomal rearrangements. Altogether 23/26 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the two novel somatic rearrangements ETV6-NTRK3 and AGK-BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. A lower prevalence of fusion oncogenes was found in a cohort of pediatric thyroid cancers from children from the same geographical regions that were not exposed to radiation. Radiation-induced thyroid cancers are a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program. Examination of transcriptome profiles and genetic somatic changes in thyroid cancer.
Project description:Exposure to ionizing radiation during childhood markedly increases the risk of developing papillary thyroid cancer. We identified non-overlapping somatic driver mutations in all 26 cases of post-Chernobyl thyroid cancers we studied through candidate gene assays and next generation RNA-sequencing. We found that 22/26 harbored fusion oncogenes arising primarily through intrachromosomal rearrangements. Altogether 23/26 of the oncogenic drivers identified in this cohort aberrantly activate MAPK signaling, including the two novel somatic rearrangements ETV6-NTRK3 and AGK-BRAF. Two other tumors harbored distinct fusions leading to overexpression of the nuclear receptor PPARγ. A lower prevalence of fusion oncogenes was found in a cohort of pediatric thyroid cancers from children from the same geographical regions that were not exposed to radiation. Radiation-induced thyroid cancers are a paradigm of tumorigenesis driven by fusion oncogenes that activate MAPK signaling or, less frequently, a PPARγ-driven transcriptional program.
Project description:RNA-Sequencing analysis of 18 papillary thyroid carcinoma biopsies and of 4 healthy donors' thyroids. In this analysis we assessed differential gene expression and investigated the mutational landscape in this tumor type. Analysis of gene fusion was also performed, leading to the identification of a novel chimeric transcript, potential driver in tumor initiation. Total RNA isolated from 18 papillary thyroid carcinoma biopsies and 4 healthy donors' thyroids.
Project description:Purpose: The primary goal of this study was to identify gene-expression profiles of anaplastic thyroid cancer and to identify some novel in-frame gene fusions that could result in translated protein products affecting the development of anaplastic thyroid cancer. Methods: RNAseq Data was processed with TCGA UNC V2 RNAseq protocol and different expressed genes were identify by using DESeq2, limma-voom, and edgeR. Potential fusion genes were identified by using SOAPfuse, Chimerascan and TopHat-Fusion. Potential fusion genes were confirmed by cDNA PCR and Sanger sequencing. Results: A total of 21 fusion genes were detected, including six predicted in-frame fusions; none were recurrent. Global gene expression analysis showed 661 genes to be differentially expressed between anaplastic thyroid cancer and papillary thyroid cancer cell lines, with pathway enrichment analyses showing downregulation of TP53-signaling as well as cell adhesion molecules in anaplastic thyroid cancer . Conclusions: Our study represents the first detailed analysis of anaplastic thyroid cancer cell lines and found several novel in-frame gene fusions that could result in translated protein products affecting the development of anaplastic thyroid cancer. These data provide novel insights into the tumorigenesis of anaplastic thyroid cancer and may be used to identify new therapeutic targets.
Project description:Tumor microenvironment heterogeneity sheltered our understanding of papillary thyroid cancer. However, molecular characteristics of papillary thyroid cancer has not been reported at single cell resolution. The immunological link between papillary thyroid cancer and Hashimoto's thyroiditis is also in doubt.We identified 24 cell clusters in human papillary thyroid cancer based on their heterogeneous gene expression pattern. Follicular epithelial cell subsets in papillary thyroid cancer with Hashimoto's thyroiditis and papillary thyroid cancer without Hashimoto's thyroiditis showed different malignant level. Machine learning model identified potential biomarker to evaluate tumor epithelial cell development. Together with immunostaining, lymphocytes heterogeneity indicated an obvious B cell infiltration pattern in papillary thyroid cancer with Hashimoto's thyroiditis. Additionally, trajectory analysis of B cell and plasma cell suggest the migration potential from normal adjacent tissue of Hashimoto's thyroiditis to papillary thyroid cancer tissue. Our results provide the first single cell landscape of Papillary thyroid cancer. Single cell data resource of Papillary thyroid cancer with Hashimoto's thyroiditis promote our understanding of molecular heterogeneity and immunological link between papillary thyroid cancer and Hashimoto's thyroiditis.
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid thyroid papillary cancer vs. patient-matched adjacent nontumor thyroid tissues. -14 tumors from France -12 tumors from Ukraine
Project description:Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas (FTC and PTC, respectively). Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied a label-free quantitative mass spectrometry analysis to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma.
Project description:We compared the expression profiles of papillary thyroid tumors from the Chernobyl Tissues Bank (CTB) with tumors from French patients with no history of exposure to radiations. Keywords: papillary thyroid cancer vs. patient-matched healthy adjacent thyroid
Project description:Thyroid gland is among the most sensitive organs to ionizing radiation. Whether low-dose radiation-induced papillary thyroid cancer (PTC) differs from sporadic PTC is yet unknown. We used microarrays to identify gene signature of radiation-induced papillary thyroid carcinomas