AUTHOR=Didier-Mathon Hortense , Stoupa Athanasia , Kariyawasam Dulanjalee , Yde Sonny , Cochant-Priollet Beatrix , Groussin Lionel , Sébag Frédéric , Cagnard Nicolas , Nitschke Patrick , Luton Dominique , Polak Michel , Carré Aurore 

TITLE=Borealin/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1286747

DOI=10.3389/fendo.2023.1286747

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p><italic>BOREALIN</italic>/<italic>CDCA8</italic> mutations are associated with congenital hypothyroidism and thyroid dysgenesis. Borealin is involved in mitosis as part of the Chromosomal Passenger Complex. Although <italic>BOREALIN</italic> mutations decrease thyrocyte adhesion and migration, little is known about the specific role of Borealin in the thyroid.</p></sec><sec><title>Methods</title><p>We characterized thyroid development and function in Borealin-deficient (<italic>Borealin</italic><sup>+/−</sup>) mice using histology, transcriptomic analysis, and quantitative PCR.</p></sec><sec><title>Results</title><p>Thyroid development was impaired with a hyperplastic anlage on embryonic day E9.5 followed by thyroid hypoplasia from E11.5 onward. Adult <italic>Borealin</italic><sup>+/−</sup> mice exhibited euthyroid goiter and defect in thyroid hormone synthesis. <italic>Borealin</italic><sup>+/−</sup> aged mice had disorganized follicles and papillary-like structures in thyroids due to ERK pathway activation and a strong increase of <italic>Braf</italic>-like genes described by The Cancer Genome Atlas (TCGA) network of papillary thyroid carcinoma. Moreover, <italic>Borealin</italic><sup>+/−</sup> thyroids exhibited structural and transcriptomic similarities with papillary thyroid carcinoma tissue from a human patient harboring a <italic>BOREALIN</italic> mutation, suggesting a role in thyroid tumor susceptibility.</p></sec><sec><title>Conclusion</title><p>These findings demonstrate Borealin involvement in critical steps of thyroid structural development and function throughout life. They support a role for Borealin in thyroid dysgenesis with congenital hypothyroidism. Close monitoring for thyroid cancer seems warranted in patients carrying <italic>BOREALIN</italic> mutations.</p></sec>