{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:03:30Z","timestamp":1790705010426,"version":"4.1.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Sporadic medullary thyroid carcinoma (MTC) is a relatively uncommon neuroendocrine malignancy and the molecular tumorigenesis of its sporadic type (sMTC) is only partially understood. In this study, we performed a study focusing on the genomic and transcriptomic characterization of sMTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Twenty-nine sMTC patients were included. Whole-exome sequencing (WES) was carried out in 18 patients, including both tumor samples and matched noncancerous tissues. Whole transcriptome sequencing (RNA-Seq) was performed in all 29 tumors. WES, RNA-Seq, and copy number alteration (CNA) data were analyzed. A Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among the somatic mutations,\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      was the only recurrently cancer-related mutated gene (5\/18, 27.8%). In the germline,\n                      <jats:italic toggle=\"yes\">FAT1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FAT4<\/jats:italic>\n                      , two members of the FAT gene family, were identified as the two most common mutated genes. CNA analysis found that\n                      <jats:italic toggle=\"yes\">FAT1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FAT4<\/jats:italic>\n                      , both located on chromosome 4q, were also two of the genes most commonly affected by somatic chromosomal deletions (4\/18, 22.2%). Using TT and MZ-CRC-1 cell lines, the CCK-8 assay showed that\n                      <jats:italic toggle=\"yes\">FAT1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">FAT4<\/jats:italic>\n                      knockdown could promote MTC cell proliferation. Based on the gene expression profile, patients were clustered into two molecular subtypes: the mesenchymal-like subtype is characterized by epithelial\u2013mesenchymal transition, while the proliferative-like subtype is associated with enrichment of cell cycle pathways. Most events of structural recurrence (80%) occurred in the proliferative-like subtype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      In addition to\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      , these findings demonstrate that\n                      <jats:italic toggle=\"yes\">FAT1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">FAT4<\/jats:italic>\n                      genomic alterations appear to be frequent in sMTC. Two molecular subtypes of sMTC with distinct biological behavior could be identified. However, these results need to be validated by larger samples and more comprehensive experiments in the future, especially for the frequency and function of\n                      <jats:italic toggle=\"yes\">FAT1<\/jats:italic>\n                      \/\n                      <jats:italic toggle=\"yes\">FAT4<\/jats:italic>\n                      germline variants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2019.0531","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T06:08:13Z","timestamp":1581055693000},"page":"1025-1036","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Genomic and Transcriptomic Characterization of Sporadic Medullary Thyroid Carcinoma"],"prefix":"10.1177","volume":"30","author":[{"given":"Ning","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. 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China."},{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China."},{"name":"Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The First Hospital of China Medical University, China Medical University, Shenyang, P.R. 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