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This retrospective study analyzed 354 thyroid nodules from 346 patients (2018\u20132023) to investigate the clinical and pathological implications of isolated\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations and\n                    <jats:italic>RAS<\/jats:italic>\n                    with co-occurring genetic alterations. Isolated\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations were found in 41.0% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009145), while 54.8% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009194) had\n                    <jats:italic>RAS<\/jats:italic>\n                    with additional molecular alterations;\n                    <jats:italic>NRAS<\/jats:italic>\n                    was the most frequent subtype (62.1%). Among co-occurring mutations,\n                    <jats:italic>EIF1AX<\/jats:italic>\n                    (46.7%) and\n                    <jats:italic>TERT<\/jats:italic>\n                    (26.7%) were the most common, primarily in\n                    <jats:italic>NRAS<\/jats:italic>\n                    -positive cases. Surgical follow-up data from 302 cases revealed a malignancy rate of 52.3% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009158), with 60.1% (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200995) being invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC).\n                    <jats:italic>NRAS<\/jats:italic>\n                    mutations appeared in 64.6% of malignant cases. Isolated\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations were mainly associated with benign\/low-risk neoplasms (47.0%), notably follicular adenomas and encapsulated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), or malignancies (41.0%). The malignancy rate was higher in nodules with a\n                    <jats:italic>RAS<\/jats:italic>\n                    mutation plus one concomitant molecular alteration (54.3%), and nearly 100% in those with three additional genetic alterations. Co-occurring genetic alterations with\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations markedly increased the risk of malignancy compared with isolated\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations (Fisher\u2019s exact test, two-tailed\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0026) and were associated with more aggressive tumor phenotypes, whereas isolated\n                    <jats:italic>RAS<\/jats:italic>\n                    mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.\n                  <\/jats:p>","DOI":"10.1007\/s12022-026-09910-6","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:13:50Z","timestamp":1772694830000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of Co-Mutations and Genetic Variations on Malignancy Risk in RAS-Positive Indeterminate Thyroid Nodules: an Institutional Experience"],"prefix":"10.1007","volume":"37","author":[{"given":"Lawrence Q.","family":"Wong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubair W.","family":"Baloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"9910_CR1","unstructured":"National Cancer Institute (2025) Cancer Stat Facts: Thyroid Cancer. https:\/\/seer.cancer.gov\/statfacts\/html\/thyro.html. 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