{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:41:20Z","timestamp":1790797280888,"version":"4.1.0"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,12,14]]},"abstract":"<jats:p>\n                    Lymphangioleiomyomatosis (LAM) is a multisystem disorder of women, characterized by cystic degeneration of the lungs, renal angiomyolipomas (AML), and lymphatic abnormalities. LAM lesions result from the proliferation of benign-appearing, smooth muscle-like LAM cells, which are characterized by loss of heterozygosity (LOH) of one of the tuberous sclerosis complex (TSC) genes. LAM cells are believed to migrate among the involved organs. Because of the apparently metastatic behavior of LAM, we tried to isolate LAM cells from body fluids. A cell fraction separated by density gradient centrifugation from blood had\n                    <jats:italic>TSC2<\/jats:italic>\n                    LOH in 33 of 60 (55%) LAM patients. Cells with\n                    <jats:italic>TSC2<\/jats:italic>\n                    LOH were also found in urine from 11 of 14 (79%) patients with AML and in chylous fluid from 1 of 3 (33%) patients. Identification of LAM cells with\n                    <jats:italic>TSC2<\/jats:italic>\n                    LOH in body fluids was not correlated with severity of lung disease or extrapulmonary involvement and was found in one patient after double lung transplantation. These studies are compatible with a multisite origin for LAM cells. They establish the existence of disseminated, potentially metastatic LAM cells through a relatively simple, noninvasive procedure that should be valuable for molecular and genetic studies of somatic mutations in LAM and perhaps other metastatic diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0407971101","type":"journal-article","created":{"date-parts":[[2004,12,6]],"date-time":"2004-12-06T20:24:54Z","timestamp":1102364694000},"page":"17462-17467","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":159,"title":["Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis"],"prefix":"10.1073","volume":"101","author":[{"given":"Denise M.","family":"Crooks","sequence":"first","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Pacheco-Rodriguez","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosamma M.","family":"DeCastro","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"J. Philip","family":"McCoy","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-an","family":"Wang","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyuki","family":"Kumaki","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Darling","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Moss","sequence":"additional","affiliation":[{"name":"Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892; and Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,12,6]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.54.3.254"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.115.4.1041"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.18500"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4065\/75.6.591"},{"key":"e_1_3_2_5_2","first-page":"669","volume":"163","year":"2001","unstructured":"Moss, J., Avila, N. 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