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Germline Mutations in Familial Papillary Thyroid Cancer


Thyroid cancer, predominantly of papillary histology (PTC), is a common cancer mostly diagnosed sporadically. Hereditary PTC is encountered in ~ 5% of cases and may present at an earlier age, with greater risks of metastasis and recurrence, compared with sporadic cases. The molecular basis of hereditary PTC is unknown in most cases. In this study, the genetic basis of hereditary PTC in three Brazilian families was investigated. Whole exome sequencing (WES) was carried out for probands in each family, and validated, pathogenic/likely pathogenic sequence variants (P/LPSVs) were genotyped in additional family members to establish their putative pathogenic role. Overall, seven P/LPSVs in seven novel genes were detected: p.D283N*ANXA3, p.Y157S*NTN4, p.G172W*SERPINA1, p.G188S*FKBP10, p.R937C*PLEKHG5, p.L32Q*P2RX5, and p.Q76*SAPCD1. These results indicate that these novel genes are seemingly associated with hereditary PTC, but extension and validation in other PTC families are required.

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We thank all family members for their support.


This work was partially funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq No. 405053/2013-4) and CAPES, Brazil

Author information

Marta Sarquis and Debora C. Moraes contributed equally to this manuscript.

Correspondence to Luiz De Marco.

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The experimental protocols were approved by the Institutional Review Board at the Universidade Federal de Minas Gerais (ETIC 367/07).

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Sarquis, M., Moraes, D.C., Bastos-Rodrigues, L. et al. Germline Mutations in Familial Papillary Thyroid Cancer. Endocr Pathol (2020). https://doi.org/10.1007/s12022-020-09607-4

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  • Hereditary papillary thyroid carcinoma
  • Whole exome sequencing
  • Inherited predisposition
  • Candidate genes