The role of EIF1AX in thyroid cancer tumourigenesis and progression

  • J. Simões-Pereira
  • M. M. Moura
  • I. J. Marques
  • M. Rito
  • R. A. Cabrera
  • V. Leite
  • B. M. Cavaco
Original Article



The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. Our aim was to address whether EIF1AX mutations are present in the different stages of thyroid tumourigenesis (from hyperplasia to well-differentiated and to poorly differentiated/undifferentiated lesions), and to clarify its role in this process.


We analysed the EIF1AX gene in a series of 16 PDTC and ATC cases with coexistent well-differentiated regions and/or benign lesions. In EIF1AX mutant cases we also assessed the presence of RAS genes mutations.


We identified the mutation p.Ala113_splice in the EIF1AX gene in two PDTCs (neither present in the well-differentiated counterparts nor in the benign areas). One of these tumours also evidenced the mutation p.Glu61Arg in NRAS in both poorly and well-differentiated regions, further suggesting that the EIF1AX p.Ala113_splice mutation could be associated with tumoural progression. In another patient we did not find any EIF1AX alteration in the PDTC component, but we detected the EIF1AX p.Gly6_splice mutation in the PTC area (both regions were RAS wild-type). This mutation did not seem to be related with dedifferentiation.


According to our results, distinct mutations on EIF1AX may be related to different phenotypes/behaviours. Despite being a small series, which reflects the difficulty in retrieving PDTC and ATC surgical samples with well-differentiated and/or benign areas, our study may provide new insights into thyroid cancer tumourigenesis and dedifferentiation.


EIF1AX Thyroid cancer RAS Poorly differentiated thyroid cancer Anaplastic thyroid cancer 



The authors are thankful for the collaboration of the Endocrinology and Pathology Departments, from Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Lisboa, Portugal.


This work was funded by Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo (SPEDM), Associação de Endocrinologia Oncológica (AEO), by Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), and by iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundação para a Ciência e Tecnologia/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. Joana Simões-Pereira was supported by iNOVA4Health, and Inês J. Marques was a recipient of a PhD fellowship from the PhD Programme ProRegeM (Mechanisms of Disease and Regenerative Medicine) approved by Fundação para a Ciência e Tecnologia—PD/BD/108086/2015.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interests.

Ethical approval

This study involved histological specimens from patients that were collected following local institution guidelines. This study was approved by the Ethical Committee of Instituto Português de Oncologia de Lisboa Francisco Gentil.

Informed consent

Consent forms were signed, except for those who had died, in agreement with the Ethical Committee of Instituto Português de Oncologia de Lisboa Francisco Gentil.


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Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  1. 1.Serviço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  2. 2.Unidade de Investigação em Patobiologia Molecular (UIPM)Instituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  3. 3.NOVA Medical School, Faculdade de Ciências MédicasUniversidade Nova de LisboaLisboaPortugal
  4. 4.Centro de Estudos de Doenças Crónicas (CEDOC)LisboaPortugal
  5. 5.Serviço de Anatomia PatológicaInstituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal

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