High-resolution 400K oligonucleotide array comparative genomic hybridization analysis of neurofibromatosis type 1-associated cutaneous neurofibromas

Neurofibromatosis type 1 (NF1) is a genetic disorder where affected individuals develop benign or malignant nervous system tumors. To date, NF1 is caused by mutations in the NF1 tumor suppressor gene located at chromosome band 17q11.2. In this study, we aimed to characterize novel recurrent regional chromosomal imbalances and tumor-related candidate genes in NF1-associated cutaneous neurofibromas. Nine cutaneous neurofibromas from NF1 patients were screened for recurrent chromosomal imbalances using high-resolution 400K oligonucleotide array comparative genomic hybridization (aCGH). All the cases exhibited at least one sub-microscopic abnormality. Regions of recurrent chromosomal imbalances in a least one third of cases were loss of 1q13.2 (33%, FAM19A3), 1q21.1 (44%, RABGAP1L), 2q37.1 (56%, INPP5D), 3p25.1 (67%, CHCHD4), 4p15.32 (56%, FGFBP1), 5q11.2 (56%, ARL15), 6q22.31 (56%, NKAIN2), 6q22.33 (67%, ARHGAP18), 6q25.1 (67%, UST), 7q13 (56%, ADCY1), 12q13.13 (44%, KRT71), 19q13.32 (56%, GRLF1), and 20p11.21 (56%, NLP) and gain of 2p23.3 (76%, C2orf53), 8q22.3 (44%, ODF1) and 8q24.3 (67%, ARC). Several chromosomal imbalances, including loss of 7q11.23, 13q14.1, 14q32.13, 17p12, and 17q11.2 were detected at a lower frequency. We also confirmed that these chromosomal imbalances were not detected in the patient-matched lymphocyte DNAs. Amongst the 6 tumor-related candidate genes (RABGAP1L, ADCY1, SLIT2, GRLF1, UST, and ARC) identified in the regions of recurrent chromosomal imbalances, the gene expression changes of UST (down-regulation) and ARC (up-regulation) were found to be significantly associated with copy number alterations. The novel recurrent chromosomal imbalances and the altered expression levels of the tumor-related candidate genes may be associated with the development of NF1-associated benign cutaneous neurofibromas. •We provide 400K oligo-aCGH data in NF1-associated cutaneous neurofibromas (cNF).•Identification of novel recurrent regions of chromosomal imbalances in the cNF•These chromosomal imbalances are not detected in patient-matched lymphocyte DNAs.•We report novel candidate genes involved in the pathogenesis of cNF.