R C Yu1, A C Chu. 1. Unit of Dermatology, Royal Postgraduate Medical School, London, United Kingdom.
Abstract
BACKGROUND: Studies using X-chromosome inactivation assays have recently provided evidence in support of a clonal origin of cells affected by Langerhans cell histiocytosis (LCH). A search for more specific clonal markers has led to the investigation for T-cell receptor (TCR) gene rearrangements in cells affected by LCH. METHODS: Conventional southern blot analysis was used to investigate the possibility of clonal TCR gene rearrangements in tissues affected by LCH wherever possible, otherwise, a polymerase chain reaction (PCR)-based technique was employed for amplification of rearranged joint (J) and variable (V) segments of the TCR-gamma gene including the N-region. 32P-labeled PCR products were then resolved using nondenaturing polyacrylamide gel electrophoresis. RESULTS: The results using the PCR-based technique showed a lack of clonal rearrangement of the TCR-gamma gene in affected tissues of eight patients with different stages of LCH. Southern blot analyses performed on two of these samples confirmed germline configurations at both the TCR-C-beta and delta-2 gene loci. CONCLUSIONS: There is no evidence of clonal TCR gene rearrangement in cells involved by LCH. The search for a more specific clonal marker to address whether "'LCH cells" represent a neoplastic clonal transformation of cells with differentiation toward Langerhans cell phenotype continues.
BACKGROUND: Studies using X-chromosome inactivation assays have recently provided evidence in support of a clonal origin of cells affected by Langerhans cell histiocytosis (LCH). A search for more specific clonal markers has led to the investigation for T-cell receptor (TCR) gene rearrangements in cells affected by LCH. METHODS: Conventional southern blot analysis was used to investigate the possibility of clonal TCR gene rearrangements in tissues affected by LCH wherever possible, otherwise, a polymerase chain reaction (PCR)-based technique was employed for amplification of rearranged joint (J) and variable (V) segments of the TCR-gamma gene including the N-region. 32P-labeled PCR products were then resolved using nondenaturing polyacrylamide gel electrophoresis. RESULTS: The results using the PCR-based technique showed a lack of clonal rearrangement of the TCR-gamma gene in affected tissues of eight patients with different stages of LCH. Southern blot analyses performed on two of these samples confirmed germline configurations at both the TCR-C-beta and delta-2 gene loci. CONCLUSIONS: There is no evidence of clonal TCR gene rearrangement in cells involved by LCH. The search for a more specific clonal marker to address whether "'LCH cells" represent a neoplastic clonal transformation of cells with differentiation toward Langerhans cell phenotype continues.