Spectral karyotypic and comparative genomic analysis of the endocrine pancreatic tumor cell line BON-1.
BON-1 is a human serotonin-producing endocrine pancreatic tumor (EPT) cell line, which has been used for various studies of tumorigenesis and treatment. Because its genotype, phenotype and degree of differentiation may underlie events that are instrumental to the development of endocrine tumors and, moreover, may vary between labs and over time, we decided to comprehensively characterize the chromosomal constitution of BON-1 by applying conventional GTG-banding, spectral karyotyping (SKY), comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). BON-1 cells proved to be hyperdiploid containing a modal chromosome number of 57 (range 56-64). SKY identified a stemline containing 6 clonal aberrations including del(1p), t(9;12)del(9p)x2, der(10)t(5;10), der(19)t(8;19), der(14)t(9;14)t(9;10), and a sideline harboring an additional del(12q). CGH and FISH confirmed the SKY results and, in addition, highlighted the chromosomal regions involved in the rearrangements. Moreover, they identified a homozygous deletion of the key tumor suppressor genes CDKN2A and CDKN2B at 9p21.3, in accordance with absence of p16(INK4A) and p14(ARF) expression as revealed by immunocytochemistry. Apart from deregulation of the cell cycle and p53 pathway this finding indicates escape from replicative senescence (induced by mutated NRAS) and detachment-induced apoptosis as molecular mechanisms underlying the tumorigenesis of BON-1 cells. Immunostaining results for p53, MDM2 and pRb expression were consistent with previously published data using Western analysis. In conclusion, we provide here a comprehensive cytogenetic profile of BON-1. This cell line harbors both numerical and structural genomic alterations indicative for malignant EPTs.
Lopez
Juan R
JR
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Claessen
Sandra M H
SM
Macville
Merryn V E
MV
Albrechts
Jozefa C M
JC
Skogseid
Britt
B
Speel
Ernst-Jan M
EJ
D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002871:Chromosome Banding; D019457:Chromosome Breakage; D055028:Comparative Genomic Hybridization; D004701:Endocrine Gland Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007515:Islets of Langerhans; D010190:Pancreatic Neoplasms / Q000235:genetics*; D032681:Spectral Karyotyping; D014178:Translocation, Genetic
D015415:Biomarkers