TY - JOUR
T1 - 20q gain associates with immortalization
T2 - 20q13.2 amplification correlates with genome instability in human papillomavirus 16 E7 transformed human uroepithelial cells
AU - Savelieva, Elena
AU - Belair, Cassandra D.
AU - Newton, Michael A.
AU - DeVries, Sandy
AU - Gray, Joe W.
AU - Waldman, Frederic
AU - Reznikoff, Catherine A.
N1 - Funding Information:
We would like to thank Joan S Kozel of UW Hospital Medical Illustration Department for her help with the color FISH photos. This work was supported by NIH R01 CA29525-16 and R01 CA67158-02 to CAR and by a kind gift from the Haertle Family to the University of Wisconsin Comprehensive Cancer Center.
PY - 1997
Y1 - 1997
N2 - Breast, bladder, colon, and ovarian carcinomas show frequent low level 20q gain and less frequently high level 20q13.2 amplification, but the significance of these 20q amplifications in transformation has not been defined. Using karyotypic and comparative genomic hybridization (CGH) analyses, chromosome losses and gains were analysed in six newly immortalized human uroepithelial cell (HUG) lines transformed by Human Papillomavirus 16 (HPV16) E7. Results showed clonal chromosomes with 20q11- > qter gain in all six lines. CGH revealed a peak of 20q13.2 amplification in two cell lines. FISH with whole chromosome 20 paint showed expanded chromosome regions (ECRs) and double minute chromosomes (DMs) that contained chromosome 20 material in cell lines with 20q13.2 amplification. FISH with probes from the center of the 20q13.2 human breast cancer amplicon showed as many as 24 signals in cells with 20q13.2 amplification. The acquisition of genome instability in these E7-HUCs did not correlate with TP53 mutation, as all E7-HUCs contained only wildtype TP53. These results suggest that low level 20q gain is associated with overcoming cellular senescence in E7 transformed cells (P-value = 2 x 10-7), but does not confer genome instability, while high level 20q13.2 amplification is associated with chromosome instability. Loss of 10p (P-value = 3 x 10-5) was also important in immortalization of E7-transformed HUCs. Thus, these results have profound implications for interpreting the significance of high versus low level 20q gains in human cancers.
AB - Breast, bladder, colon, and ovarian carcinomas show frequent low level 20q gain and less frequently high level 20q13.2 amplification, but the significance of these 20q amplifications in transformation has not been defined. Using karyotypic and comparative genomic hybridization (CGH) analyses, chromosome losses and gains were analysed in six newly immortalized human uroepithelial cell (HUG) lines transformed by Human Papillomavirus 16 (HPV16) E7. Results showed clonal chromosomes with 20q11- > qter gain in all six lines. CGH revealed a peak of 20q13.2 amplification in two cell lines. FISH with whole chromosome 20 paint showed expanded chromosome regions (ECRs) and double minute chromosomes (DMs) that contained chromosome 20 material in cell lines with 20q13.2 amplification. FISH with probes from the center of the 20q13.2 human breast cancer amplicon showed as many as 24 signals in cells with 20q13.2 amplification. The acquisition of genome instability in these E7-HUCs did not correlate with TP53 mutation, as all E7-HUCs contained only wildtype TP53. These results suggest that low level 20q gain is associated with overcoming cellular senescence in E7 transformed cells (P-value = 2 x 10-7), but does not confer genome instability, while high level 20q13.2 amplification is associated with chromosome instability. Loss of 10p (P-value = 3 x 10-5) was also important in immortalization of E7-transformed HUCs. Thus, these results have profound implications for interpreting the significance of high versus low level 20q gains in human cancers.
KW - 20q amplification
KW - Genome instability
KW - HPV16 E7
KW - Human uroepithelial cells
KW - Immortalization
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U2 - 10.1038/sj.onc.1200868
DO - 10.1038/sj.onc.1200868
M3 - Article
C2 - 9053853
AN - SCOPUS:0031054750
SN - 0950-9232
VL - 14
SP - 551
EP - 560
JO - Oncogene
JF - Oncogene
IS - 5
ER -