title: Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism.
abstract: Lymphangiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells and cystic degeneration of the lung. LAM affects almost exclusively young women. Although lung transplantation provides effective therapy for end-stage LAM, there are reports of LAM recurrence after lung transplantation. Whether these recurrent LAM cells arise from the patient or the lung transplant donor is an area of controversy. We used microsatellite marker fingerprinting and TSC2 gene mutational analysis to study a patient with recurrent LAM after single-lung transplantation. The DNA microsatellite marker pattern indicated the presence of patient-derived LAM cells in the allograft. A somatic one base pair deletion in exon 18 of the TSC2 gene was identified in pulmonary and lymph node LAM cells before transplantation. The same mutation was in the recurrent LAM, demonstrating that the recurrent LAM was derived from the patient. Fluorescence in situ hybridization revealed that cells immunoreactive with the monoclonal antibody HMB-45 did not contain a Y chromosome. These data indicate that histologically benign LAM cells can migrate or metastasize in vivo to the transplanted lung. In addition, the patient had no evidence of a renal angiomyolipoma at autopsy and therefore demonstrated for the first time that somatic TSC2 mutations cause LAM in patients without angiomyolipomas.
authors.affiliation: Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Karbowniczek
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Astrinidis
authors.forename: Binaifer R
authors.initials: BR
authors.lastname: Balsara
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Testa
authors.forename: James H
authors.initials: JH
authors.lastname: Lium
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colby
authors.forename: Francis X
authors.initials: FX
authors.lastname: McCormack
authors.forename: Elizabeth Petri
authors.initials: EP
authors.lastname: Henske
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008168:Lung; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary / Q000601:surgery*; D016040:Lung Transplantation; D008198:Lymph Nodes; D018192:Lymphangioleiomyomatosis / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D018895:Microsatellite Repeats / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000209:etiology* / Q000235:genetics / Q000556:secondary; D011183:Postoperative Complications / Q000209:etiology; D012097:Repressor Proteins / Q000235:genetics; D017211:Treatment Failure; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins