TY - JOUR
T1 - Spectral Karyotypic and Comparative Genomic Analysis of the Endocrine Pancreatic Tumor Cell Line BON-1
AU - Lopez, Juan R.
AU - Claessen, Sandra M. H.
AU - Macville, Merryn V. E.
AU - Albrechts, Jozefa C. M.
AU - Skogseid, Britt
AU - Speel, Ernst-Jan M.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - BON-1
KW - Endocrine pancreatic tumor
KW - Carcinoid
KW - Spectral karyotyping
KW - Comparative genomic hybridization
KW - p16(INK4A)
U2 - 10.1159/000254483
DO - 10.1159/000254483
M3 - Article
C2 - 19887762
SN - 0028-3835
VL - 91
SP - 131
EP - 141
JO - Neuroendocrinology
JF - Neuroendocrinology
IS - 2
ER -