AUTHOR=Du Yaying , Zhang Shu , Zhang Gang , Hu Jiaying , Zhao Lianhua , Xiong Yuanyuan , Shen Lu , Chen Rongrong , Ye Ke , Xu Yan 

TITLE=Mutational profiling of Chinese patients with thyroid cancer

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1156999

DOI=10.3389/fendo.2023.1156999

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>The incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed.</p></sec><sec><title>Methods</title><p>We retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel.</p></sec><sec><title>Results</title><p>A total of 458 Chinese patients with thyroid cancer were enrolled, including four malignant histological subtypes arising from follicular epithelial thyroid cells. <italic>BRAF</italic> driver mutations were identified in 76.0% of patients, followed by <italic>RET</italic> rearrangements (7.6%) and <italic>RAS</italic> driver mutations (4.1%). Tumors with more somatic mutations correlated with worse clinical characteristics, including older age at diagnosis, less differentiation of tumor, larger tumor size, lymph node metastasis and distal metastasis. Subclonal <italic>BRAF</italic> mutations occurred in 20% (6/30) of patients and were frequent in poorly differentiated or anaplastic tumors (33.3% [2/6] vs. 4.2% [1/24], <italic>P</italic> = 0.09) and those with distal metastasis (50.0% [2/4] vs. 8.7% [2/23], <italic>P</italic> = 0.09). Tumors with <italic>TERT</italic> promoter mutations had significantly more somatic mutations (average: 6.5 vs. 1.8, <italic>P</italic> &lt; 0.001). Moreover, <italic>TERT</italic> promoter mutations were not associated with lymph node metastasis but significantly associated with older age at diagnosis and poorly differentiated or anaplastic tumors, regardless of their clonal architecture.</p></sec><sec><title>Conclusion</title><p>Our results shed light on the molecular pathogenesis and clinical characteristics of thyroid cancer in the Chinese population. The number of somatic mutations, <italic>TERT</italic> promoter mutations, and the clonal architecture of <italic>BRAF</italic> mutations should be considered in the risk stratification of thyroid cancer.</p></sec>