title: Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis.
abstract: 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 TSC2 LOH in 33 of 60 (55%) LAM patients. Cells with TSC2 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 TSC2 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.
authors.affiliation: Pulmonary-Critical Care Medicine Branch and Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Crooks
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-Rodriguez
authors.forename: Rosamma M
authors.initials: RM
authors.lastname: DeCastro
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Ji-an
authors.initials: JA
authors.lastname: Wang
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Kumaki
authors.forename: Thomas
authors.initials: T
authors.lastname: Darling
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
mesh_terms: D001826:Body Fluids / Q000166:cytology; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity / Q000235:genetics; D018192:Lymphangioleiomyomatosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D015898:Tomography Scanners, X-Ray Computed; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins