Project description:The study involves whole transcriptome sequencing of 30 orphan FFPE tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the expression profile, fusion genes and pathogen profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into transcriptomic alterations prevalent in Indian anaplastic thyroid carcinoma.
Project description:The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with very high mortality. Double-stranded RNA–directed RNA interference (dsRNAi) targeting the PIAS2 isoform beta (PIAS2b) inhibits growth of ATC cell lines and patient primary cultures in vitro and orthotopic patient-derived xenografts (oPDX) in vivo, but not of thyroid cell lines or non-anaplastic primary thyroid cultures (differentiated carcinoma, benign lesions, or normal). PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. Strikingly, PIAS2b-dsRNAi induces mitotic catastrophe at prophase. High-throughput proteomics revealed the proteasome (PSMC5) and spindle cytoskeleton as direct targets of PIAS2b SUMOylation at mitotic initiation. PIAS2b-dsRNAi is a promising therapy for ATC and other aggressive anaplastic cancers.
2024-04-08 | PXD044110 | Pride
Project description:Genomic Profiling of Anaplastic/Undifferentiated Thyroid Carcinoma
| PRJNA1072836 | ENA
Project description:RNA based Transcriptomic fusion gene analysis in Poorly Differentiated Thyroid carcinoma
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:Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. We have engineered the first mouse model of ATC by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion and distant metastases. We have performed expression profiling of thyroids from control, single mutants, compound mutants, follicular tumors from Pten-/- mice, and anaplastic tumors from Pten, p53-/- mice.
Project description:We performed 4D-DIA proteomic profiling on formalin-fixed paraffin-embedded (FFPE) thyroid tissues, covering anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and matched normal (N) controls. Using the timsTOF Pro platform with ion mobility–enhanced DIA, we systematically quantified global protein expression across tumor subtypes. The dataset provides high-quality spectral data and processed protein quantitation matrices, enabling comparative analyses of thyroid cancer progression from differentiated to undifferentiated states. This resource supports biomarker discovery and mechanistic exploration in thyroid cancer biology.
Project description:Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. We have engineered the first mouse model of ATC by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion and distant metastases.
Project description:The study involves targeted sequencing of 30 orphan FFPE tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the mutation profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into genomic alterations prevalent in Indian anaplastic thyroid carcinoma.
Project description:The study involves whole exome sequencing of 38 orphan primary tumors obtained from anaplastic thyroid carcinoma patients of Indian origin. With this, we aim to describe the mutational profile of this specific subset of anaplastic thyroid cancer patients. This knowledge will further allow us to gain an insight into potentially actionable genomic alterations prevalent in Indian anaplastic thyroid carcinoma.