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Germline Mutations in Familial Papillary Thyroid Cancer

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Abstract

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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Acknowledgments

We thank all family members for their support.

Funding

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

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Author notes

  1. Marta Sarquis and Debora C. Moraes contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Marta Sarquis

  2. Department of Surgery, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Debora C. Moraes, Pedro G. Azevedo, Fabiana Versiani Reis, Paula V. Dande, Isabela Paim & Luiz De Marco

  3. Department of Nutrition, Faculdade de Enfermagem, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Luciana Bastos-Rodrigues

  4. Hospital Felicio Rocho, Belo Horizonte, Brazil

    Adauto V. Ramos

  5. The Suzanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Eitan Friedman

  6. The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Eitan Friedman

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  1. Marta Sarquis
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Contributions

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

Corresponding author

Correspondence to Luiz De Marco.

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Ethics Statement

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 31, 14–20 (2020). https://doi.org/10.1007/s12022-020-09607-4

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