Abstract
Ascertaining the driving factors and molecular flow through that confiscate favorable to aggressive high-risk disease has momentous importance in neuroblastoma cure. Herein, we investigated the cytogenetic and tumorigenic/metastatic physiognomies of distinct population of highly malignant (NBP4) cells established from multi-site aggressive tumors after parental (SH-SY5Y) cell xenotransplantation. Karyotyping (G-banding) NBP4 revealed 47 (XX) with six novel non-random chromosomal rearrangements on 1q32, 8p23, 9q34, 15q24, 22q13 (additions), and 7q32 (deletion). Compared to the parental cells, high-resolution array CGH analysis of NBP4 cells and aggressive tumors revealed genetic alterations in chromosomes 1, 7, 8 and 22 corresponding to gain in coding regions of LOC100288142, CD1C, CFHR3, FOXP2, MDFIC, RALYL, CSMD3, SAMD12-AS1, MAL2 and loss in coding regions of ADAM5, LOC400927, APOBEC3B, RPL3, MGAT3, SLC25A17, EP300, L3MBTL2, SERHL, POLDIP3, A4GALT and TTLL1. Compared to SH-SY5Y cells, aggressive NBP4 cells exert stem-like phenotype and under stem-cell-growth conditions demonstrated a profound tumorosphere forming capabilities. Moreover, xenotransplantation of NBP4 cells exhibited high tumor forming capacity and metastatic potential in vivo. Together, these data demonstrate the clonal enrichment of select highly malignant cells drives neuroblastoma progression, and further implies that observed genetic alterations could mediate phenotypic transformation and functional response.
Citation Format: Faizan H. Khan, Satish K. Ramraj, Vijayabaskar Pandian, Sheeja Aravindan, Terence S. Herman, Mohan Natarajan, Natarajan Aravindan. Non-random genetic rearrangements driven highly malignant tumor-cell population dictates the development of high-risk neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2238. doi:10.1158/1538-7445.AM2014-2238
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