Dominant genetic alterations in immortalization: Role for 20q gain

Abstract

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 × 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. © 1999 Wiley‐Liss, Inc.

The identification of chromosome abnormalities associated with the invasive phenotype of uveal melanoma in vitro

“…It is however of interest that a translocationaffecting chromosome 20 in SOM 196 was rapidly lost from invasive variants, possibly targeting relevant genes on chromosome 20. It has been suggested that specific genes on chromosome 20 may play a role in allowing cultured cells to bypass senescence [17]. Immortalisation of human uroepithelial cells with human papillomavirus 16 (HPV 16) E7 is associated with non-random accumulation of chromosome 20 material, either by low level gain of chromosome 20q, or amplification of 20q13.2, suggesting the presence of a dominant immortalising gene on chromosome 20.…”

Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

“…The gain of chromosome 20 observed in all the immortalized cell line is indeed intriguing. Low copy number gain of chromosome 20 has previously been reported to be associated with cellular immortalization by viral oncoproteins and hTERT [44][45][46][47]. These results suggest that the gain of this chromosome might contribute to immortalization.…”

The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors

“…Other than chromosome 20q gain per se, this amplification was associated with genomic instability, despite retention of wild-type p53 [23]. Interestingly, both 20q gain and 20q13.2 amplification have been reported for various cancer types [33] including UC [34–36], where amplifications of chromosome 20q generally appear to be associated with immortalization, oncogenic transformation and malignant progression. Whereas high level amplifications correlated with tumor progression in breast cancer [37], low-level amplifications appeared to be rather associated with early stage ovarian carcinoma [38].…”