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No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies
Author(s) -
da Costa Cristiana E. T.,
Szuhai Karoly,
van Eijk Ronald,
Hoogeboom Manja,
Sciot Raphael,
Mertens Fredrik,
Björgvinsdóttir Helga,
DebiecRychter Maria,
de Krijger Ronald R.,
Hogendoorn Pancras C. W.,
Egeler R. Maarten,
Annels Nicola E.
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20634
Subject(s) - langerhans cell histiocytosis , biology , karyotype , comparative genomic hybridization , ploidy , exon , microbiology and biotechnology , genomic dna , chromosomal translocation , gene , snp array , genetics , pathology , single nucleotide polymorphism , chromosome , genotype , disease , medicine
Abstract 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 multiparameter 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 CD1a‐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. © 2008 Wiley‐Liss, Inc.