{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:54Z","timestamp":1753869714022,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T00:00:00Z","timestamp":1644019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is an inherited cystic kidney disease associated with a spectrum of various renal and extrarenal manifestations, including increased risk of kidney cancers. Here, we present the initial molecular description of sarcomatoid renal cell carcinoma (sRCC) arising in the setting of ADPKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiregion whole\u2010exome sequencing and whole transcriptomic sequencing were used to examine intratumoral molecular heterogeneity among histologically\u2010distinct spindle (sarcomatoid), epithelioid, or biphasic compartments within the tumor and compared with the non\u2010malignant ADPKD component.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Spindle and biphasic components harbored several overlapping driver gene mutations, but do not share any with the epithelioid component. Mutations in <jats:italic>ATM<\/jats:italic>, <jats:italic>CTNNB1<\/jats:italic>, and <jats:italic>NF2<\/jats:italic> were present only in the biphasic and spindle components, while mutations in <jats:italic>BID<\/jats:italic>, <jats:italic>FLT3<\/jats:italic>, <jats:italic>ARID1B<\/jats:italic>, and <jats:italic>SMARCA2<\/jats:italic> were present only in the epithelioid component. We observed dichotomous evolutionary pathways in the development of epithelioid and spindle compartments, involving early mutations in <jats:italic>TP53<\/jats:italic> and <jats:italic>ATM<\/jats:italic>\/<jats:italic>CTNNB1<\/jats:italic>\/<jats:italic>NF2<\/jats:italic> respectively. Wnt, PI3K\u2010mTOR, and MAPK signaling pathways, known key mechanisms involved in ADPKD development, featured prominently in the sarcomatoid component.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This highlights that common pro\u2010oncogenic signals are present between ADPKD and sRCC providing insights into their shared pathobiology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1853","type":"journal-article","created":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T08:39:57Z","timestamp":1644050397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiregion sequencing of sarcomatoid renal cell carcinoma arising from autosomal dominant polycystic kidney disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Elizabeth","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Medical Oncology National Cancer Centre Singapore  Singapore 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