Project description:Discrimination between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) prior to surgery remains a major challenge in clinical practice. To evaluate the feasibility of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs for non-invasive detection of FTC. The diagnostic properties of sEV long RNAs, cell-free long RNAs, sEV miRNAs, and cell-free miRNAs were compared for the detection of FTC.
Project description:Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). Methods Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. Results All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). Conclusions We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research.
Project description:Minimally invasive follicular thyroid carcinoma (MI-FTC) is characterized by limited capsular and/or vascular invasion with good long-term outcomes. However, some cases of MI-FTC show a poor prognosis because of severe distant metastasis. Nonetheless, no method has been established for predicting the prognosis of MI-FTC. This study was conducted to identify novel prognostic factors for metastatic MI-FTC by use of the formalin-fixed paraffin-embedded (FFPE) specimens of this carcinoma.
Project description:Fallopian tube carcinoma (FTC) is a rare, poorly studied and aggressive cancer, associated with poor survival. Since tumorigenesis is related to acquisition of genetic changes, we used genome-wide array CGH to analyze copy number aberrations occurring in FTC in order to obtain a better understanding of FTC carcinogenesis and to identify prognostic events and targets for therapy. We used arrays of 2464 genomic clones, providing ~1.4 Mb resolution across the genome to quantitatively map genomic DNA copy number aberrations from fourteen FTC onto the human genome sequence. All tumors showed a high frequency of copy number aberrations with recurrent gains on 3q, 6p, 7q, 8q, 12p, 17q, 19 and 20q, and losses involving chromosomes 4, 5q, 8p, 16q, 17p, 18q and X. Recurrent regions of amplification included 1p34, 8p11-q11, 8q24, 12p, 17p13, 17q12-q21, 19p13, 19q12-q13 and 19q13. Candidate, known oncogenes mapping to these amplicons included CMYC (8q24), CCNE1 (19q12-q21) and AKT2 (19q13), whereas PIK3CA and KRAS, previously suggested to be candidate driver genes for amplification mapped outside copy number maxima on 3q and 12p, respectively. The FTC were remarkably homogeneous, with some recurrent aberrations occurring in more than 70% of samples, which suggests a stereotyped pattern of tumor evolution. Keywords: array CGH, CCNE1, AKT2, Fallopian tube cancer
Project description:Poorly differentiated thyroid carcinomas (PDTC) represent a heterogeneous, aggressive entity, presenting features that suggest a progression from well-differentiated carcinomas. To elucidate the mechanisms underlying such progression and identify novel therapeutical targets, we assessed the genome-wide expression in normal thyroid tissues, well-differentiated thyroid carcinomas and PDTC. RNA were extracted from 2 normal thyroid tissues taken from the opposite lobe of thyroid tumors, and 24 thyroid carcinomas: 5 PDTC, 7 classic papillary thyroid carcinomas (cPTC), 8 follicular variants of PTC (fvPTC) and 4 follicular thyroid carcinomas (FTC). All samples were obtained at time of surgery and immediately frozen in liquid nitrogen. We also hybridized a commercial pool of human thyroid total RNA (BD Bioscience). PTC were screened for BRAF mutations and rearrangements of RET/PTC and, in addition, follicular variants were also analyzed for RAS mutations and PAX8-PPARG rearrangements. FTC were screened for RAS and PAX8-PPARG rearrangements. PDTC were analyzed for BRAF, RAS and PAX8-PPARG genes.
Project description:Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for the differential diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples.
Project description:Understanding cellular processes underlying early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here, we performed whole exome sequencing (WES) of human treatment-naive lungs comprising various stages in the sequence of pathogenesis of LUAD including normal lung tissues, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and LUAD.
Project description:Identifying high-risk follicular thyroid cancer (FTC) is critical for stratified treatment and developing targeted therapies. This study performed RNA sequencing on high-risk FTC, identifying Carbonic Anhydrase 12 (CA12) as a promising biomarker. High CA12 expression predicted poor disease-free survival, surpassing conventional markers. In vitro, CA12 knockdown reduced proliferation and invasion, while a CA12 inhibitor showed synergistic anti-proliferative effects with Lenvatinib. These findings establish CA12 as both a novel prognostic biomarker and a potential therapeutic target for FTC.
Project description:We aimed to decipher APOBEC3A driven mutational differences in human PDX_PDAC tissues. 40 human PDX_PDAC tissues were grouped based on their APOBEC3A expression levels into APOBEC3A High and Low groups. Illumina whole exome sequencing (WES) was performed and downstream variant analysis was applied.