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Consistent Amyloid Fibril Structures Across Multiple Organs and Patients in ATTRv-T60A Amyloidosis Revealed by Cryo-EM

ABSTRACT: Cardiac ATTRv-T60A amyloid fibrils from three different patients, and ATTRv-T60A fibrils from thyroid, explanted kidney, and explanted liver from one of the patients (tissues obtained from autopsy and transplant surgery). Identification of tryptic and non-tryptic fragments in ATTRv-V30M). Cardiac ATTR fibrils (patient 1): Sample ID: 1176938 Cardiac ATTR fibrils (patient 2): Sample ID: 1176937 Cardiac ATTR fibrils from (patient 3): Sample ID: 1176932 Thyroid ATTR fibrils from (patient 3): Sample ID: 1176934 Renal ATTR fibrils from (patient 3): Sample ID: 1176933 Hepatic ATTR fibrils from (patient 3): Sample ID: 1176935

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Lorena Saelices Gomez

PROVIDER: MSV000095675 | MassIVE | Thu Aug 22 13:14:00 BST 2024

REPOSITORIES: MassIVE

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Project description:Well-differentiated tumours (WDT) of the thyroid gland can be difficult to diagnose. Focal nuclear clearing can be suggestive of a papillary thyroid carcinoma (PTC), while questionable vascular or capsular penetration may raise the possibility of diagnosis of a follicular thyroid carcinoma (FTC). The recently proposed term “thyroid tumours of uncertain malignant potential” (TT-UMP) defines cases showing inconclusive morphological evidence of malignancy. We use microRNA (miRNA) expression profiling to analyze 42 well differentiated thyroid tumours including 7 follicular tumours of uncertain malignant potential (FT-UMP), 6 well differentiated tumours of uncertain malignant potential (WDT-UMP), 7 follicular thyroid adenomas (FTA), 5 follicular variant of papillary thyroid carcinoma (FV-PTC) 6 follicular thyroid carcinoma (FTC), and 11 conventional papillary thyroid carcinoma (C-PTC) with 6 C-PTC mutated for BRAFV600E (C-PTC-mut) and 5 not mutated: wild type (C-PTC-wt). Comparison of these 13 tumours of uncertain malignant potential (7 FT-UMP and 6 WDT-UMP) with those obtained from 16 PTC (11 C-PTC and 5 FV-PTC), 6 FTC and 7 FTA is performed in order to clarify the relationships between TT-UMP and the morphologically well characterized categories of thyroid tumours (i.e. C-PTC, FV-PTC, FTC and FTA). In first, each pathological sample (“L” for Lesional tissue) is compared with its matched control (“S” for Safe tissue) for the 42 patients (84 miRNA microarray slides). This control was taken from the same patient at a large distance from the tumour. Secondly, the perilesional tissue from the same patients but 2 (1 PTC and 1 adenoma, without enough RNA left) is compared to normal thyroid tissue (safe tissue reference) obtained from a patient who underwent total thyroidectomy for a laryngeal carcinoma that partially invaded the thyroid gland, to search for microRNA signatures of perilesional tissues (80 miRNA microarray slides).Experiments is performed with a miRNA microarray, referenced in GEO under the accession number GPL4717 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL4717). 42 Patients: 7 FT-UMP, 6 WDT-UMP, 7 FTA (+1 duplicate sample), 5 FV-PTC, 6 FTC (+ 2 duplicate samples), and 11 C-PTC. 44 dye-swap pairs and 1 with no dye swap pair for a total of 89 samples.

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Consistent Amyloid Fibril Structures Across Multiple Organs and Patients in ATTRv-T60A Amyloidosis Revealed by Cryo-EM

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