Whole-genome sequencing of follicular thyroid carcinomas reveal recurrent mutations in microRNA processing subunit DGCR8

SND-ID: 2021-108

Description Data and documentation

Creator/Principal investigator(s)

Christofer Juhlin - Karolinska Institutet, Department of Oncology-Pathology orcid

Johan Paulsson - Karolinska Institutet, Department of Oncology-Pathology

Description

Background
The genomic and transcriptomic landscape of widely invasive follicular thyroid carcinomas (wiFTCs) is poorly characterized, and a large subset of these tumours lack information on credible genetic driver events. The aim of this study was to bridge this gap.
Methods
We performed whole-genome and RNA sequencing and subsequent bioinformatic analyses of 13 wiFTCs with a particularly poor prognosis, and matched normal tissue.
Results
Ten out of thirteen (77%) tumours exhibited one or several mutations in established genes ranked as the top 20 mutated in thyroid cancer, including TERT (n=4), NRAS (n=3), HRAS, KRAS, AKT, PTEN, PIK3CA, MUTYH and MEN1 (n=1 each). Recurrent somatic mutations in three genes were annotated as significant according to MutSig2CV: FAM72D (n=3), TP53 (n=3) and EIF1AX (n=3), with DGCR8 (n=2) as borderline significant. Of interest, both DGCR8 mutations were recurrent p.E518K missense alterations, a mutation known to cause familial multinodular goiter (MNG) via disruption of microRNA (miRNA) processing. Expression analyses pinpointed a trend towards reduced DGCR8 mRN

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Language

English

Research principal, contributors, and funding

Research principal

Karolinska Institutet

Contributor(s)

Yi Chen - Karolinska Institutet, Department of Oncology-Pathology

Sebastian DiLorenzo - Uppsala University, Department of Medical Biochemistry and Microbiology / Department of Cell and Molecular Biology

Nima Rafati - Uppsala University, Department of Medical Biochemistry and Microbiology / Department of Cell and Molecular Biology

Jan Zedenius - Karolinska Institutet, Department of Molecular Medicine and Surgery orcid

Felix Haglund - Karolinska Institutet, Department of Oncology-Pathology

Protection and ethical review

Data contains personal data

Yes

Sensitive personal data

Yes

Ethics Review

Stockholm - Ref. Dnr 2015/959-31

Method

Population

The study included 13 patients with follicular thyroid carcinoma. All diagnosed at the Karolinska University Hospital, Stockholm.

Study design

Experimental study

Description of study design

Whole-genome and RNA sequencing of 13 tumor and normal tissue pairs.

Biobank is connected to the study

This study has used existing samples from a scientific collection or biobank

Scientific collection or biobank name: KI Biobank

Type(s) of sample: tumor tissue

Geographic coverage

Geographic spread

Geographic location: Sweden

Publications
Dataset
Whole-genome sequencing of follicular thyroid carcinomas reveal recurrent mutations in microRNA processing subunit DGCR8

Description

The dataset consists of tables and lists containing underlying data, and supplementary figures for a manuscript submitted to "Journal of Clinical Endocrinology & Metabolism". It includes 8 tables and 3 figures:

File name: T1_Detailed-characteristics-of-the-study-cohort.csv
Contains "Table 1: Detailed characteristics of the study cohort." 

File name: T2_List-of-Somatic-SNVs.csv
Contains "Table 2: List of Somatic SNV's (Small nucleotide variants)." 

File name: T3_MutSig2CV-input-genes.csv
Cont

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Version 1

Citation

Christofer Juhlin, Johan Paulsson. Karolinska Institutet, Department of Oncology-Pathology (2021). <em>Whole-genome sequencing of follicular thyroid carcinomas reveal recurrent mutations in microRNA processing subunit DGCR8</em>. Swedish National Data Service. Version 1. <a href="https://doi.org/10.5878/6fcv-1795">https://doi.org/10.5878/6fcv-1795</a>

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Data format / data structure

Text

Still image

Creator/Principal investigator(s)

Christofer Juhlin - Karolinska Institutet, Department of Oncology-Pathology orcid

Johan Paulsson - Karolinska Institutet, Department of Oncology-Pathology

Data collection

  • Mode of collection: Measurements and tests
  • Source of the data: Biological samples

Number of individuals/objects

13

Contact for questions about the data

Published: 2021-06-24