LAUSR

BACKGROUND Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans Cell Histiocytosis (PLCH) are cystic lung diseases in which a neoplastic cell is believed to be responsible for disease pathogenesis. The neoplastic LAM cell has mutations in the Tuberous Sclerosis Complex (TSC) genes, TSC1 or TSC2, whereas the neoplastic PLCH cell may have mutations in several genes, e.g., BRAF, NRAS, MAP2K1. These mutations are not specific for PLCH and they have been described in multiple cancers. TSC1 or TSC2 mutations and loss of heterozygosity (LOH) have also been described in cancers. RESEARCH QUESTION Is TSC2 LOH specific to LAM or is it also found in PLCH too? STUDY DESIGN We recruited LAM patients (53) and Healthy Volunteers (22) and compared the presence of cells with TSC2 LOH with PLCH patients (12). Blood and urine samples were collected for analysis. METHODS Fluorescence-activated cell sorting (FACS) was used to identify subpopulations of cells from blood and urine samples. We isolated CD45-CD235a-, CD45-CD235a+, CD45+CD235a- cells from blood following density gradient separation. Cells were screened for TSC2 LOH at 5 microsatellites markers (i.e., kg8, D16S3395, D16S3024, D16S521, D16S291). We obtained four cell subpopulations from urine (i.e., CD44v6+CD9+; CD44v6+CD9-; CD44v6-CD9+; CD44v6-CD9). RESULTS Using FACS, cells were isolated from blood and urine from PLCH patients that showed TSC2 LOH. Healthy volunteers did not have cells with TSC2 LOH. As a control, cells isolated from blood and urine from LAM patients gave results similar to those reported previously. These data show that TSC2 LOH is found in patients with cystic lung diseases with potential neoplastic characteristics, as well as in patients with cancer. INTERPRETATION The presence of TSC2 LOH in circulating cells is not specific for LAM. The data suggest that chromosomal abnormalities affecting the TSC2 gene are found in other diseases associated with cells having cancer-like neoplastic cells.