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The role of EIF1AX in thyroid cancer tumourigenesis and progression

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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.

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  1. Fagin JA, Wells SA Jr (2016) Biologic and clinical perspectives on thyroid cancer. N Engl J Med 375:1054–1067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Cancer Genome Atlas Research Network (2014) Integrated genomic characterization of papillary thyroid carcinoma. Cell 159:676–690

    Article  CAS  Google Scholar 

  3. Kunstman JW, Juhlin CC, Goh G, Brown TC, Stenman A, Healy JM et al (2015) Characterization of the mutational landscape of anaplastic thyroid cancer via whole-exome sequencing. Hum Mol Genet 24:2318–2329

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH et al (2016) Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 126:1052–1066

    Article  PubMed  PubMed Central  Google Scholar 

  5. Karunamurthy A, Panebianco F, Hsiao JS, Vorhauer J, Nikiforova MN, Chiosea S et al (2016) Prevalence and phenotypic correlations of EIF1AX mutations in thyroid nodules. Endocr Relat Cancer 23:295–301

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Pita JM, Figueiredo IF, Moura MM, Leite V, Cavaco BM (2014) Cell cycle deregulation and TP53 and RAS mutations are major events in poorly differentiated and undifferentiated thyroid carcinomas. J Clin Endocrinol Metab 99:E497–E507

    Article  PubMed  CAS  Google Scholar 

  7. Etemadmoghadam D, Azar WJ, Lei Y, Moujaber T, Garsed DW, Kennedy CJ et al (2017) EIF1AX and NRAS mutations co-occur and cooperate in low-grade serous ovarian carcinomas. Cancer Res 77:4268–4278

    Article  PubMed  CAS  Google Scholar 

  8. Jung SH, Kim MS, Jung CK, Park HC, Kim SY, Liu J et al (2016) Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma. Oncotarget 7:69638–69648

    PubMed  PubMed Central  Google Scholar 

  9. Topf MC, Wang ZX, Furlong K, Miller JL, Tuluc M, Pribitkin EA (2018) EIF1AX mutation in a patient with Hürthle Cell Carcinoma. Endocr Pathol 29:27–29

    Article  PubMed  CAS  Google Scholar 

  10. Kohlmann A, Klein HU, Weissmann S, Bresolin S, Chaplin T, Cuppens H et al (2011) The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories. Leukemia 25:1840–1848

    Article  PubMed  CAS  Google Scholar 

  11. Ewens KG, Kanetsky PA, Richards-Yutz J, Purrazzella J, Shields CL, Ganguly T et al (2014) Chromosome 3 status combined with BAP1 and EIF1AX mutation profiles are associated with metastasis in uveal melanoma. Invest Ophtalmol Vis Sci 55:5160–5167

    Article  CAS  Google Scholar 

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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.

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Correspondence to B. M. Cavaco.

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The authors have no conflict of interests.

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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.

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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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Simões-Pereira, J., Moura, M.M., Marques, I.J. et al. The role of EIF1AX in thyroid cancer tumourigenesis and progression. J Endocrinol Invest 42, 313–318 (2019).

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