TY - JOUR
T1 - No genomic aberrations in langerhans cell histiocytosis as assessed by diverse molecular technologies
AU - Da Costa, Cristiana E.T.
AU - Szuhai, Karoly
AU - Van Eijk, Ronald
AU - Hoogeboom, Manja
AU - Sciot, Raphael
AU - Mertens, Fredrik
AU - Björgvinsdóttir, Helga
AU - Debiec-Rychter, Maria
AU - De Krijger, Ronald R.
AU - Hogendoorn, Pancras C.W.
AU - Maarten Egeler, R.
AU - Annels, Nicola E.
PY - 2009/3
Y1 - 2009/3
N2 - The etiology of Langerhans cell histiocytosis (LCH), a disease characterized by uncontrolled proliferation of Langerhans cells, is unknown. Although some believe that LCH is reactive, others support a neoplastic origin. We tested the hypothesis that LCH is neoplastic by investigating potential consistent chromosomal aberrations in LCH cells. We used multipara-meter DNA flow cytometry to analyze the DNA ploidy LCH cells in 20 cases, performed karyotype analysis in 31 cases, array-based comparative genomic hybridization (arrayCGH) and single nucleotide polymorphism (SNP) arrays with DNA from flow-sorted CD1 a-positive and CD1a-negative cells in 19 cases. Ploidy analysis revealed diploid DNA content in all cases. The karyotype of all patients analyzed was normal, excluding the presence of balanced translocations. ArrayCGH and SNP arrays did not show genome abnormalities. Despite positive TP53 protein immunohistochemical staining, sequencing of exon 5 to 8 of p53 gene showed no alterations in 7 cases. This study strongly suggests that gross chromosomal abnormalities do not cause LCH. Although we cannot exclude cryptic point mutations in as yet unidentified genes, this study of 72 LCH cases shows that LCH may be the result of restricted oligoclonal stimulation rather than unlimited neoplastic proliferation.
AB - The etiology of Langerhans cell histiocytosis (LCH), a disease characterized by uncontrolled proliferation of Langerhans cells, is unknown. Although some believe that LCH is reactive, others support a neoplastic origin. We tested the hypothesis that LCH is neoplastic by investigating potential consistent chromosomal aberrations in LCH cells. We used multipara-meter DNA flow cytometry to analyze the DNA ploidy LCH cells in 20 cases, performed karyotype analysis in 31 cases, array-based comparative genomic hybridization (arrayCGH) and single nucleotide polymorphism (SNP) arrays with DNA from flow-sorted CD1 a-positive and CD1a-negative cells in 19 cases. Ploidy analysis revealed diploid DNA content in all cases. The karyotype of all patients analyzed was normal, excluding the presence of balanced translocations. ArrayCGH and SNP arrays did not show genome abnormalities. Despite positive TP53 protein immunohistochemical staining, sequencing of exon 5 to 8 of p53 gene showed no alterations in 7 cases. This study strongly suggests that gross chromosomal abnormalities do not cause LCH. Although we cannot exclude cryptic point mutations in as yet unidentified genes, this study of 72 LCH cases shows that LCH may be the result of restricted oligoclonal stimulation rather than unlimited neoplastic proliferation.
UR - http://www.scopus.com/inward/record.url?scp=62449241914&partnerID=8YFLogxK
U2 - 10.1002/gcc.20634
DO - 10.1002/gcc.20634
M3 - Article
C2 - 19051326
AN - SCOPUS:62449241914
SN - 1045-2257
VL - 48
SP - 239
EP - 249
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 3
ER -