Novel Structural Abnormalities Involving Chromosomes 1, 17 and 2 Identified by Fluorescence In Situ Hybridization (FISH) and/or Cytogenetic Karyotyping in Kelly and SH-SY5Y Human Neuroblastoma Cell Lines, Respectively

Abstract

Abstract: MYCN amplification and 1p36 deletion are important poor prognostic factors in neuroblastoma. 1p36 deletion and unbalanced translocations involving chromosomes 1, 17 and 2p were often reported in neuroblastoma cell lines. We aimed to investigate novel chromosomal abnormalities that are likely to affect neuroblastoma progression in Kelly and SH-SY5Y cell lines. Therefore, we analyzed the metaphase chromosomes using fluorescence in situ hybridization (FISH) method with probes specific to the chromosome bands 2p24 and 1p36 in SH-SY5Y and Kelly, respectively. Moreover, the rearrangements of chromosomes 1 and 17 from Kelly were re-examined by cytogenetic karyotyping. FISH analysis shows duplication of chromosome 2p24 on the long arm of a partner chromosome resulted from an unbalanced translocation der(?9)t(2;?9)(p24;q?34) in SH-SY5Y, suggesting that duplication of 2p24 locus containing MYCN gene may contribute to triggering MYCN amplification in neuroblastoma. On the other hand, FISH and karyotype analyses reveal three copies of chromosome 1 that consist of an intact chromosome 1, an extra derivative chromosome 1 with terminal and interstitial deletions (:p32→q25::q41→qter), and another including only interstitial deletion (pter→q25::q41→qter), leading to monosomy of the long arm segment 1q25-q41 in Kelly. These results suggest that chromosome 1q25-q41 may contain one or more tumour suppressor genes important for neuroblastoma progression. Together, FISH analysis shows that an additional 1p36 locus in Kelly is translocated to the short arm of extra chromosome 17, where the p53 tumour suppressor gene is located. Consequently, these novel structural abnormalities involving chromosomes 1, 17 and 2 could be contributed to the tumourigenicity of neuroblastoma cells.