Analyzing the Role of DICER1 Germline Variations in Papillary Thyroid Carcinoma

Sule Canberk; Joana C Ferreira; Luísa Pereira; Rui Batısta; Andre F Vieira; Paula Soares; Manuel Sobrinho Simões; Valdemar Máximo

doi:10.1159/000509183

Analyzing the Role of DICER1 Germline Variations in Papillary Thyroid Carcinoma

Eur Thyroid J. 2021 Feb;9(6):296-303. doi: 10.1159/000509183. Epub 2020 Aug 6.

Authors

Sule Canberk^{1

2

3}, Joana C Ferreira^{1

2}, Luísa Pereira^{1

2

4}, Rui Batısta^{1

2}, Andre F Vieira^{1

2}, Paula Soares^{1

2

4}, Manuel Sobrinho Simões^{1

2

4

3

5}, Valdemar Máximo^{1

2

4}

Affiliations

¹ Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
² Institute of Molecular Pathology and Immunology of the University of Porto (Ipatimup), Porto, Portugal.
³ Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
⁴ Department of Pathology, Faculty of Medicine of the University of Porto (FMUP), Porto, Portugal.
⁵ Department of Pathology and Oncology, Centro Hospitalar São João, Porto, Portugal.

Abstract

Introduction: DICER1 is a member of RNase III family that has a pivotal role in the biogenesis of microRNAs, being important for normal development. Dysregulation of DICER1 has been described in different human tumours; however, there is insufficient data on the risk of thyroid cancer in the presence of germline DICER1 variants, particularly when focusing on the background of papillary thyroid carcinoma (PTC). For this purpose, we ascertained the presence of DICER1 variants in 502 (PTC) cases available from The Cancer Genome Atlas (TCGA) research network in a well-characterized pathological context.

Material and methods: in this study we analyzed 502 samples from 502 patients, described as PTC in the TCGA database. Tumour diagnoses were re-evaluated by 2 pathologists (S.C. and M.S.-S.) on slides available from the database, and clinicopathological and demographic data was examined. Data concerning germline and sporadic DICER1 gene variants as well as frequent mutations in the genes involved in thyroid carcinogenesis (e.g., RAS and BRAFV600E) was retrieved from the database.

Results and discussion: We report 1 new germline possibly pathogenic variant, besides 15 others already been identified in ClinVar. We found that the DICER1-positive PTC group more frequently includes PTC variants, namely the oncocytic, follicular, and aggressive (hobnail variant of PTC) variants. A previous association of DICER1 had been demonstrated, mainly with the follicular variant of PTC and follicular thyroid carcinomas. Tumours harbouring germline DICER1 mutations were more frequently "bilateral" and "encapsulated." The frequent association of DICER1 germline variants with other mutations associated with thyroid cancer can reflect an haploinsufficiency tumour suppressor gene function of DICER1, as suggested from the study of animal models.

Keywords: DICER1; Familial thyroid disease; Germline variants; Paediatric thyroid nodules; Papillary thyroid carcinoma; Somatic mutation; Syndromic thyroid disease; Thyroid.