PMID- 10534765
OWN - NLM
STAT- MEDLINE
DCOM- 20000201
LR  - 20171116
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 26
IP  - 4
DP  - 1999 Dec
TI  - Dominant genetic alterations in immortalization: role for 20q gain.
PG  - 304-11
AB  - Gain of 20q has been observed in many cancer types, including bladder cancers. 
      However, the biological significance of low-copy-number 20q gain in human cancer 
      pathogenesis has not yet been defined. We reported that immortalization of human 
      uroepithelial cells (HUC) transformed with human papillomavirus 16 (HPV 16) E7 is 
      associated with single-copy 20q gain (P = 2 x 10(-7)). We also observed 20q13.2 
      amplification in some cell lines, but only after 20 passages. Thus, we 
      hypothesized that low-copy gain of 20q gene(s) contributes in a dominant way to 
      bypassing HUC senescence. To test this hypothesis, we fused precrisis 
      E7-transformed HUCs (pcE7s) with three independent immortal E7-HUCs that acquired 
      a single-copy 20q gain at immortalization. In one of these lines, a single-copy 
      gain of 20q and a 10p12.1-pter loss were the only cytogenetic alterations. 
      Immortal cell hybrids were obtained with all three crosses. Southern analysis for 
      unique HPV16 insertion sites, as well as fluorescence in situ hybridization 
      (FISH) with whole chromosome 20 painting probes (WCP20) for marker chromosomes in 
      the immortal clones, confirmed the hybrid and independent nature of 
      representative immortal clones. In contrast, when we used the same protocol, no 
      immortal somatic cell hybrids were obtained when HPV16 E6 immortal HUC (E6-HUC) 
      that showed 3p and 9p losses, but no 20q gain, were fused with precrisis 
      E6-transformed HUC (pcE6s). This latter observation is consistent with many 
      results demonstrating that recessive changes are required for cell 
      immortalization. Therefore, the new results reported herein for the first time 
      demonstrate that dominant changes can contribute to bypassing senescence, and 
      that such genes may be located on 20q. Genes Chromosomes Cancer 26:304-311, 1999.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Cuthill, S
AU  - Cuthill S
AD  - Department of Human Oncology, University of Wisconsin Medical School, Madison, 
      Wisconsin, USA.
FAU - Agarwal, P
AU  - Agarwal P
FAU - Sarkar, S
AU  - Sarkar S
FAU - Savelieva, E
AU  - Savelieva E
FAU - Reznikoff, C A
AU  - Reznikoff CA
LA  - eng
GR  - R01 CA29525-18/CA/NCI NIH HHS/United States
GR  - R01 CA67158-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cell Transformation, Viral/*genetics
MH  - Cells, Cultured
MH  - Cellular Senescence/genetics
MH  - Chromosomes, Human, Pair 20/*genetics
MH  - Epithelial Cells
MH  - Gene Amplification
MH  - Genes, Dominant/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Oncogene Proteins, Viral/genetics
MH  - Papillomaviridae/genetics
MH  - Papillomavirus E7 Proteins
MH  - Ureter
MH  - Virus Integration/genetics
EDAT- 1999/10/27 00:00
MHDA- 1999/10/27 00:01
CRDT- 1999/10/27 00:00
PHST- 1999/10/27 00:00 [pubmed]
PHST- 1999/10/27 00:01 [medline]
PHST- 1999/10/27 00:00 [entrez]
AID - 10.1002/(SICI)1098-2264(199912)26:4<304::AID-GCC4>3.0.CO;2-1 [pii]
PST - ppublish
SO  - Genes Chromosomes Cancer. 1999 Dec;26(4):304-11.