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.
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 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:A comparison of profiles of normal thryoid tissue (NT), papillary thyroid carcinoma tissue (PTC) and anaplastic thyroid carcinoma tissue (ATC) was carried out to identify expression patterns specifically associated with analplastic thyroid carcinoma Keywords: Expression profile survey of normal tissue and tumor subtypes
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.
