Format

Send to

Choose Destination
Clin Endocrinol (Oxf). 2017 Oct;87(4):394-399. doi: 10.1111/cen.13375. Epub 2017 Jun 19.

Identification of somatic TERT promoter mutations in familial nonmedullary thyroid carcinomas.

Author information

1
Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
2
Chronic Diseases Research Centre (CEDOC), Universidade Nova de Lisboa, Lisboa, Portugal.
3
Nova Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
4
Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
5
Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
6
Serviço de Genética, Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal.
7
Serviço de Anatomia Patológica, Instituto Português de Oncologia do Porto Francisco Gentil, Porto, Portugal.
8
Departamento de Patologia e Imunologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.

Abstract

OBJECTIVE:

The genes causing familial nonmedullary thyroid carcinoma (FNMTC) identified to date are only involved in a small fraction of the families. Recently, somatic mutations in TERT promoter region and in EIF1AX gene were reported in thyroid tumours of undefined familial status. The aim of this study was to investigate the role of TERT and EIF1AX mutations in familial thyroid tumours.

DESIGN:

The promoter region of TERT was sequenced in leucocyte DNA of the probands from 75 FNMTC families. In thyroid tumours from 54 familial cases, we assessed somatic TERT promoter, RAS and BRAF hotspot mutations, and the whole EIF1AX gene.

RESULTS:

No potentially pathogenic germline variants were identified in TERT in the 75 FNMTC families' probands. In the 54 carcinomas, we identified five cases (9%) with hotspot somatic TERT promoter mutations. BRAF mutations were found in 41% of the tumours. All TERT-positive samples were also positive for BRAF p.Val600Glu, and this co-occurrence was found to be statistically significant (P=.008). RAS mutations were detected in four tumours wild-type for TERT (7%). Evaluation of tumour mutation data together with the patients' clinicopathological features revealed a significant correlation between TERT plus BRAF mutations and advanced tumour stage (T4) (P=.020). No mutations were identified in EIF1AX.

CONCLUSIONS:

The results of this study suggest that TERT promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology. However, we show for the first time that TERT alterations are associated with familial thyroid tumour progression. Our data also suggest that TERT mutations are more often found in concomitance with BRAF mutations in advanced stages of FNMTC.

KEYWORDS:

BRAF ; RAS ; EIF1AX ; Familial nonmedullary thyroid carcinoma; TERT promoter mutations

PMID:
28502101
DOI:
10.1111/cen.13375
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center