, Volume 63, Issue 1, pp 94–100 | Cite as

Absence of EIF1AX, PPM1D, and CHEK2 mutations reported in Thyroid Cancer Genome Atlas (TCGA) in a large series of thyroid cancer

  • Ali S. AlzahraniEmail author
  • Avaniyapuram Kannan Murugan
  • Ebtesam Qasem
  • Meshael M. Alswailem
  • Balgees AlGhamdi
  • Yosra Moria
  • Hindi Al-Hindi
Original Article



The Thyroid Cancer Genome Atlas (TCGA) was a major project that significantly clarified the key underlying genetic aberrations in papillary thyroid cancer. It confirmed the previously known somatic mutations and gene fusions and disclosed additional genetic alterations that were previously unknown. Among the most significant novel genetic mutations were those in EIF1AX, PPM1D, and CHEK2.


We sought to determine the rates of these novel genetic alterations in a large sample of our patients to test the prevalence, reproducibility, and significance of these findings.

Patients and methods

We studied thyroid cancer (TC) tumor tissues from 301 unselected patients using polymerase chain reaction (PCR) and direct Sanger sequencing. DNA was isolated from paraffin-embedded formalin-fixed tumor tissue. Exons and exon–intron boundaries harboring the previously reported mutations in TCGA were amplified using PCR and directly sequenced.


We found only one of the 301 tumors (0.3%) harboring A113_splice site mutation at the intron 5/exon 6 splice site of EIF1AX gene. Apart from this single mutation, none of the 301 tumors harbored any of the previously reported mutations in any of the three genes, EIF1AX, PPM1D, and CHEK2. A number of previously reported single nucleotide polymorphisms (SNP) were found in CHEK2, PPM1D but not in EIF1AX. These include CHEK2 SNPs, rs375130261, rs200928781, rs540635787, rs142763740, and rs202104749. The PPM1D SNPs rs771831676 and rs61757742 were present in 1.49% and 0.74%, respectively. Each of these SNPs was present in a heterozygous form in 100% of the tumors. An additional analysis of these samples for the most frequently reported mutations in DTC such as BRAFV600E, TERT promoter, and RAS showed a prevalence of 38.87% (117/301), 11.96% (36/301), and 7.64% (23/301), respectively.


Except for a rare A113_splice site mutation in EIF1AX, other recently described somatic mutations in EIF1AX, PPM1D, and CHEK2 were absent in this large series of patients with TC from a different racial group (Saudi Arabia). This might be related to the different techniques used (PCR and direct sequencing) or low density of the mutants. It might also reflect racial differences in the rate of these mutations.


Thyroid cancer Mutations TCGA Thyroid Cancer Genome Atlas 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This study was performed only on archived pathology samples and did not obtain any new samples from the patients. With that and according to the Institutional Review Board rules and guidelines, informed consents were waived by the Institutional Review Board of the King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ali S. Alzahrani
    • 1
    • 2
    Email author
  • Avaniyapuram Kannan Murugan
    • 1
  • Ebtesam Qasem
    • 1
  • Meshael M. Alswailem
    • 1
  • Balgees AlGhamdi
    • 3
  • Yosra Moria
    • 2
  • Hindi Al-Hindi
    • 4
  1. 1.Department of Molecular OncologyKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  2. 2.Department of MedicineKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  3. 3.Research Centre-JeddahKing Faisal Specialist Hospital & Research CentreJeddahSaudi Arabia
  4. 4.Department of Laboratory Medicine and PathologyKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia

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