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:Objective: This study aimed to investigate SETDB2 expression, clinical significance, and molecular mechanism in thyroid cancer progression. Methods: SETDB2 expression and prognosis were analyzed using TCGA and CPTAC databases, and validated by immunohistochemistry in 90 clinical samples (primary, recurrent, metastatic papillary, and anaplastic carcinoma). Overexpression and knockdown models were established in BCPAP and BHT101 cells. Proliferation was assessed by CCK‑8, colony formation, and EdU assays. RNA‑seq and qPCR identified downstream targets, with rescue experiments via U2AF1 overexpression. Results: SETDB2 was significantly downregulated in recurrent and metastatic papillary and anaplastic thyroid carcinoma, and low expression correlated with poor prognosis. SETDB2 overexpression suppressed proliferation and colony formation in anaplastic BHT101 cells, whereas knockdown promoted growth in papillary BCPAP cells. U2AF1 was identified as a key downstream target, and its overexpression partially reversed the inhibitory effects of SETDB2 on proliferation. Conclusion: SETDB2 acts as a tumor suppressor in thyroid cancer; its loss promotes progression, likely through regulating U2AF1. The SETDB2‑U2AF1 axis represents a potential therapeutic target.
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.
