{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:06:49Z","timestamp":1791202009463,"version":"4.2.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,5,23]]},"abstract":"<jats:p>\n                    Lymphangioleiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex. Renal angiomyolipomas, which are found in most tuberous sclerosis patients, also occur in 60% of sporadic LAM patients. We previously found\n                    <jats:italic>TSC2<\/jats:italic>\n                    loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic\n                    <jats:italic>TSC2<\/jats:italic>\n                    mutations in five of seven angiomyolipomas from sporadic LAM patients. In all four patients from whom lung tissue was available, the same mutation found in the angiomyolipoma was present in the abnormal pulmonary smooth muscle cells. In no case was the mutation present in normal kidney, morphologically normal lung, or lymphoblastoid cells. Our data demonstrate that somatic mutations in the\n                    <jats:italic>TSC2<\/jats:italic>\n                    gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of\n                    <jats:italic>TSC2<\/jats:italic>\n                    in the pathogenesis of this disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.11.6085","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"6085-6090","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":566,"title":["Mutations in the tuberous sclerosis complex gene\n                    <i>TSC2<\/i>\n                    are a cause of sporadic pulmonary lymphangioleiomyomatosis"],"prefix":"10.1073","volume":"97","author":[{"given":"Thomas","family":"Carsillo","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristotelis","family":"Astrinidis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Petri","family":"Henske","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,5,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199011013231807"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.6.1689"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.155.4.9105053"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199909000-00004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610243351704"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.107.1.189"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)61196-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/oso\/9780195122107.003.0002","volume-title":"Tuberous Sclerosis Complex","author":"Gomez M","year":"1999","unstructured":"M Gomez Tuberous Sclerosis Complex, eds M Gomez, J Sampson, V Whittemore (Oxford Univ. 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