{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:07:33Z","timestamp":1784304453532,"version":"3.55.0"},"reference-count":36,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in\n              <jats:italic>RET<\/jats:italic>\n              oncogene, and lower-frequency alterations are reported in\n              <jats:italic>KRAS<\/jats:italic>\n              and\n              <jats:italic>BRAF<\/jats:italic>\n              . Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>MATERIALS AND METHODS<\/jats:title>\n            <jats:p>\n              Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of\n              <jats:italic>RET<\/jats:italic>\n              novel mutation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Mutational landscape analysis shows expected\n              <jats:italic>RET<\/jats:italic>\n              mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like\n              <jats:italic>KRAS<\/jats:italic>\n              ,\n              <jats:italic>HRAS<\/jats:italic>\n              ,\n              <jats:italic>SF3B1<\/jats:italic>\n              , and\n              <jats:italic>BRAF<\/jats:italic>\n              to be altered only in the\n              <jats:italic>RET<\/jats:italic>\n              -negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the\n              <jats:italic>RET<\/jats:italic>\n              -negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po.23.00622","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T19:59:25Z","timestamp":1715889565000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["<i>RET<\/i>\n            Alterations Differentiate Molecular Profile of Medullary Thyroid 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