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

SND-ID: 2021-108

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

Responsible department/unit

Department of Oncology-Pathology

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

Code key exists

Yes

Ethics Review

Stockholm - Ref. Dnr 2015/959-31

Method and time period

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

Associated documentation

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 (2021). Whole-genome sequencing of follicular thyroid carcinomas reveal recurrent mutations in microRNA processing subunit DGCR8. Swedish National Data Service. Version 1. https://doi.org/10.5878/6fcv-1795

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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

Published: 2021-06-24