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Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

ABSTRACT: Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

PROVIDER: PRJNA550100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9409630_1.fastq.gz	Fastqsanger.gz
	SRR9409630_2.fastq.gz	Fastqsanger.gz
	SRR9409640_1.fastq.gz	Fastqsanger.gz
	SRR9409640_2.fastq.gz	Fastqsanger.gz
	SRR9409650_1.fastq.gz	Fastqsanger.gz

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Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers

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Deep Sequencing Identifies Multiple Fusion Transcripts, Differentially Expressed Genes, and Generalized Immune Suppression in BRAF (V600E) mutant vs. BRAF wild-type Papillary Thyroid Carcinoma

Project description:CONTEXT: BRAF V600E mutation (BRAF-mut.) confers aggressiveness in papillary thyroid carcinoma, but unidentified genomic abnormalities may be required for full phenotypic expression. OBJECTIVE: To perform deep sequencing to identify genes differentially expressed between BRAF-mut. and BRAF-wild-type (BRAF-WT) tumors, and to compare to patient clinical status. DESIGN: BRAF-mut. and BRAF-WT tumors were identified in patients with T1N0 and with T23N1 tumors. Expression levels of genes were determined from RNA sequencing (RNA-Seq) data and fusion transcripts were detected. NanoString was used to validate the RNA-Seq data for immune genes. SETTING: Patients were seen at two sites of a major referral medical center. PATIENTS: Twenty patients were studied. BRAF-mut. patients included 9 women, 3 men; 9 were TNM stage I and 3 were stage III; 3 (25%) had lymphocytic thyroiditis. BRAF-WT included 5 women; 3 men; all were stage I; 5 (62.5%) had lymphocytic thyroiditis. RESULTS: 560 of 13,085 genes were differentially expressed by RNA-Seq, and MetaCore analysis identified 55 immune function genes that were differentially expressed as a function of BRAF mutational status. Immune function genes were broadly underexpressed in BRAF-mut. tumors, with only 4 genes (HLA-G, CXCL14, TIMP1, IL1RAP) more highly expressed. NanoString validated the RNA Seq data for immune genes. Eleven high confidence fusion transcripts were detected, four being inter-chromosomal and seven intra-chromosomal. CONCLUSION: BRAF-mut. papillary thyroid cancers have less expression of immune and inflammatory response genes than BRAF-WT tumors. Thirteen of 20 (65%) tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of the newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-mut. and wild-type tumors. RNA-seq was performed on 20 thyroid carcinoma tumors

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