{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T10:26:18Z","timestamp":1788603978922,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,10,8]],"date-time":"2003-10-08T00:00:00Z","timestamp":1065571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lymphangiomyomatosis (LAM) is a life\u2010threatening lung disease affecting almost exclusively young women. Histologically, LAM is characterized by the diffuse, bilateral proliferation of abnormal smooth muscle cells and cystic degeneration of the lung parenchyma. LAM can occur as an isolated disorder (sporadic LAM), or in women with tuberous sclerosis complex (TSC\u2010LAM). Patients with both sporadic LAM and TSC\u2010LAM often have benign renal angiomyolipomas. The smooth muscle cells within the angiomyolipomas are very similar to the smooth muscle cells in pulmonary LAM. Genetic data suggest that pulmonary LAM is the result of a highly unusual disease mechanism: the metastasis of benign cells. If LAM is the result of metastasis, it is remarkable that the metastasis occurs in women, but not in men. In this review, I discuss the genetic data supporting this metastatic model for LAM. The implications of the model for the functions of the <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> gene products, hamartin and tuberin, respectively, will also be considered. Hamartin and tuberin may play functional roles in the suppression of cell migration and\/or metastasis, possibly through their regulation of the small GTPase Rho. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.10252","type":"journal-article","created":{"date-parts":[[2003,10,15]],"date-time":"2003-10-15T16:54:45Z","timestamp":1066236885000},"page":"376-381","source":"Crossref","is-referenced-by-count":107,"title":["Metastasis of benign tumor cells in tuberous sclerosis complex"],"prefix":"10.1002","volume":"38","author":[{"given":"Elizabeth Petri","family":"Henske","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,10,8]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2002.120530"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.55"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205962"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.2.9911006"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.216.1.r00jl42147"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204009"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(97)90233-1"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610243351704"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2264(199601)15:1<18::AID-GCC3>3.0.CO;2-7"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.6085"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.107.1.189"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.117.5.625"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1993.tb00158.x"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/35020106"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.4065\/75.6.591"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/316951"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00091-5"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.4.2011025"},{"key":"e_1_2_2_21_1","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195122107.001.0001","volume-title":"Tuberous sclerosis complex","author":"Gomez M","year":"1999"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202678200"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20535"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.2870130411"},{"key":"e_1_2_2_25_1","first-page":"400","article-title":"Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions","volume":"59","author":"Henske EP","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_2_26_1","first-page":"1639","article-title":"Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two\u2010hit model for the pathogenesis of tuberous sclerosis tumors","volume":"151","author":"Henske EP","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.25.2899"},{"key":"e_1_2_2_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80657-1"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200208-969OC"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63843-6"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/35010550"},{"key":"e_1_2_2_33_1","first-page":"504","article-title":"Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas","volume":"58","author":"Lee JY","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.1.25"},{"key":"e_1_2_2_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12470"},{"key":"e_1_2_2_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.161.3.9904009"},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.12.1721"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.4.2101154"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.25.2889"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/321972"},{"key":"e_1_2_2_41_1","first-page":"714","article-title":"Lymphangioleiomyomatosis: recurrence after lung transplantation","volume":"13","author":"Nine JS","year":"1994","journal-title":"J Heart Lung Transplant"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.6.7767554"},{"key":"e_1_2_2_43_1","first-page":"4766","article-title":"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles","volume":"58","author":"Plank TL","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00333-6"},{"key":"e_1_2_2_45_1","first-page":"2153","article-title":"Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome inactivation and cytogenetics of a clinically benign smooth muscle proliferation","volume":"150","author":"Quade BJ","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_2_46_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.5.1709"},{"key":"e_1_2_2_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-002-8651-8"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5049"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1086\/301804"},{"key":"e_1_2_2_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.46.29301"},{"key":"e_1_2_2_51_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.1.2005004"},{"key":"e_1_2_2_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005547200"},{"key":"e_1_2_2_53_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.114.6.1689"},{"key":"e_1_2_2_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00332-4"},{"key":"e_1_2_2_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_2_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.6.1053"},{"key":"e_1_2_2_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(97)90075-7"},{"key":"e_1_2_2_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.16409"},{"key":"e_1_2_2_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.10.6097"},{"key":"e_1_2_2_60_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.8.2104095"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.10252","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.10252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T10:47:29Z","timestamp":1700218049000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.10252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,8]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,12]]}},"alternative-id":["10.1002\/gcc.10252"],"URL":"https:\/\/doi.org\/10.1002\/gcc.10252","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,8]]}}}