The role of EIF1AX in thyroid cancer tumourigenesis and progression

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The role of EIF1AX in thyroid cancer tumourigenesis and progression

Friday, 10.08.2018

The EIF1AX gene was recently described as a new thyroid cancer-related gene, and its mutations were found not only in well-differentiated tumours but also in poorly-differentiated and anaplastic carcinomas, as well as in benign lesions.

The authors aimed to evaluate EIF1AX role in thyroid cancer tumourigenesis and dedifferentiation by studying poorly-differentiated/anaplastic tumours with well-differentiated or benign counterparts. This was the first study analysing EIF1AX mutations in coexistent thyroid lesions with distinct aggressiveness, and showed that different EIF1AX mutations, corresponding to distinct protein locations, may be associated with thyroid lesions with different phenotypes/biological behaviours.


Authors and Affiliations:

Joana Simões-Pereira1,2,3, Margarida M Moura2, Inês J Marques2,3,4, Miguel Rito5, Rafael Adame Cabrera5, Valeriano Leite1,2,3, Branca Maria Cavaco2.

1 – Serviço de Endocrinologia, 2 – Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal; 3 – NOVA Medical School | Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Campo Mártires da Pátria, N.º 130, 1169-056 Lisboa; 4 – Centro de Estudos de Doenças Crónicas (CEDOC), Rua Câmara Pestana  nº6 1150-078 Lisboa; NOVA Medical School | Faculdade de Ciências Médicas da Universidade Nova de Lisboa; 5 – Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil.



Purpose: 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.

Methods: 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.

Results: 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 EIF1AXp.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.

Conclusions:  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.


Journal:  Journal of Endocrinological Investigation