Analyzing the Role of DICER1 Germline Variations in Papillary Thyroid Carcinoma.
DICER1
Familial thyroid disease
Germline variants
Paediatric thyroid nodules
Papillary thyroid carcinoma
Somatic mutation
Syndromic thyroid disease
Thyroid
Journal
European thyroid journal
ISSN: 2235-0640
Titre abrégé: Eur Thyroid J
Pays: England
ID NLM: 101604579
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
20
01
2020
accepted:
03
06
2020
entrez:
15
3
2021
pubmed:
16
3
2021
medline:
16
3
2021
Statut:
ppublish
Résumé
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. 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., 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.
Identifiants
pubmed: 33718253
doi: 10.1159/000509183
pii: etj-0009-0296
pmc: PMC7923931
doi:
Types de publication
Journal Article
Langues
eng
Pagination
296-303Informations de copyright
Copyright © 2020 by European Thyroid Association Published by S. Karger AG, Basel.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare.
Références
Cell. 2014 Oct 23;159(3):676-90
pubmed: 25417114
J Clin Endocrinol Metab. 2018 May 1;103(5):2009-2015
pubmed: 29474644
J Med Genet. 2011 Apr;48(4):273-8
pubmed: 21266384
Cell Death Differ. 2010 Apr;17(4):633-41
pubmed: 20019750
Eur J Endocrinol. 2013 Dec 21;170(2):321-7
pubmed: 24272198
Science. 2009 Aug 21;325(5943):965
pubmed: 19556464
Endocr Relat Cancer. 2016 Dec;23(12):R577-R595
pubmed: 27807061
J Clin Endocrinol Metab. 2017 May 1;102(5):1614-1622
pubmed: 28323992
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Cell Cycle. 2015;14(13):2018-21
pubmed: 26030480
Genes Dev. 2009 Dec 1;23(23):2700-4
pubmed: 19903759
Gynecol Endocrinol. 2010 Aug;26(8):617-22
pubmed: 20632913
Am J Hum Genet. 1986 Dec;39(6):811-6
pubmed: 3799599
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
JAMA. 2011 Jan 5;305(1):68-77
pubmed: 21205968
Cancer. 1999 Jun 1;85(11):2368-74
pubmed: 10357407
Cancer. 2016 Jan 15;122(2):198-206
pubmed: 26506214
Int J Cancer. 2017 Nov 15;141(10):2030-2036
pubmed: 28748527
Langenbecks Arch Surg. 2014 Feb;399(2):155-63
pubmed: 24352594
J Clin Endocrinol Metab. 2014 Jun;99(6):E1072-7
pubmed: 24617712