Introduction of a normal human chromosome 11 into a Wilms' tumor cell line controls its tumorigenic expression

Science ◽  
1987 ◽  
Vol 236 (4798) ◽  
pp. 175-180 ◽  
Author(s):  
B. Weissman ◽  
P. Saxon ◽  
Pasquale ◽  
G. Jones ◽  
A. Geiser ◽  
...  
1989 ◽  
Vol 2 (1) ◽  
pp. 12-21 ◽  
Author(s):  
Minoru Koi ◽  
Hiroyuki Morita ◽  
Hideto Yamada ◽  
Hitoshi Satoh ◽  
J. Carl Barrett ◽  
...  

Science ◽  
1991 ◽  
Vol 254 (5029) ◽  
pp. 293-295
Author(s):  
SF Dowdy ◽  
CL Fasching ◽  
D Araujo ◽  
KM Lai ◽  
E Livanos ◽  
...  

Wilms tumor has been associated with genomic alterations at both the 11p13 and 11p15 regions. To differentiate between the involvement of these two loci, a chromosome 11 was constructed that had one or the other region deleted, and this chromosome was introduced into the tumorigenic Wilms tumor cell line G401. When assayed for tumor-forming activity in nude mice, the 11p13-deleted, but not the 11p15.5-p14.1-deleted chromosome, retained its ability to suppress tumor formation. These results provide in vivo functional evidence for the existence of a second genetic locus (WT2) involved in suppressing the tumorigenic phenotype of Wilms tumor.


1995 ◽  
Vol 13 (4) ◽  
pp. 220-232 ◽  
Author(s):  
William B. Coleman ◽  
Karen D. McCullough ◽  
Gwyn L. Esch ◽  
Chris J. Civalier ◽  
Elizabeth Livanos ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3580-3580
Author(s):  
Michael Vincent Ortiz ◽  
Armaan Siddiquee ◽  
Daoqi You ◽  
Prabhjot Singh Mundi ◽  
Lianna Marks ◽  
...  

3580 Background: XPO1 is a nuclear export protein that selectively transports tumor and growth regulatory proteins out of the nucleus, thereby effectively inhibiting their function. We previously utilized the Virtual Inference of Protein-activity by Enriched Regulon analysis (VIPER) algorithm to discover that malignant rhabdoid tumors were dependent upon XPO1 inhibition and then evaluated a preclinical cohort using selinexor (KPT-330), the first-in-class selective inhibitor of nuclear export, to demonstrate that XPO1 inhibition was sufficient to cause cell cycle arrest, apoptosis, and disease control in multiple cell line and patient derived xenograft (PDXs) models. Our subsequent analysis revealed that the most common childhood kidney tumor, Wilms tumor, has even high higher inferred activity of XPO1 than rhabdoid tumors leading to our hypothesis that XPO1 inhibition is an effective therapeutic strategy to treat Wilms tumors. Methods: A panel of 9 Wilms tumor cell lines and 3 Wilms tumor PDXs were genomically characterized and tested to evaluate the pre-clinical efficacy of XPO1 inhibition in Wilms tumors. Results: Proliferation rate, increased XPO1 protein expression, and loss of function mutations in TP53 correlated with in vitro Wilms tumor cell line sensitivity to selinexor. Evaluation of co-segregation of all single nucleotide variant changes using with inferred activity of XPO1 on VIPER in all TGCA tumors demonstrates a strong association with TP53 alterations. XPO1 inhibition was effective in all Wilms tumor models tested, most significantly in MSKREN-57196, a favorable histology Wilms tumor PDX with somatic 1q gain as well as WTX and MYCN mutations, as well as in MSKREN-31827, a diffusely anaplastic TP53 mutant Wilms tumor PDX. Eltanexor (KPT-8602) is an XPO1 inhibitor with decreased CNS penetration and an improved toxicity profile; this drug was tested in these in vivo models and found to be at least as effective as selinexor. Conclusions: Somatic 1q gain in favorable histology Wilms tumors and TP53 mutations in diffusely anaplastic Wilms tumors have a particularly poor prognosis in the relapsed setting. Our study demonstrates that XPO1 inhibition may provide a rational therapeutic option to treat such high-risk Wilms tumors. Future clinical trials evaluating XPO1 inhibitors should evaluate its efficacy in children with relapsed Wilms tumors.


2012 ◽  
Vol 205 (6) ◽  
pp. 319-326 ◽  
Author(s):  
Keith W. Brown ◽  
Adrian Charles ◽  
Anthony Dallosso ◽  
Gillian White ◽  
Jessica Charlet ◽  
...  

2003 ◽  
Vol 79 (1) ◽  
pp. 151-157 ◽  
Author(s):  
Akiko Fujii ◽  
Tasuku Harada ◽  
Nobuhiro Yamauchi ◽  
Tomio Iwabe ◽  
Yoshihiro Nishi ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155561 ◽  
Author(s):  
Artur Brandt ◽  
Katharina Löhers ◽  
Manfred Beier ◽  
Barbara Leube ◽  
Carmen de Torres ◽  
...  

1993 ◽  
Vol 54 (5) ◽  
pp. 868-874 ◽  
Author(s):  
Jan Fredrik Talts ◽  
Enno Aufderheide ◽  
Lydia Sorokin ◽  
Göran Ocklind ◽  
Ragnar Mattsson ◽  
...  

1990 ◽  
Vol 42 (3) ◽  
pp. 135-142 ◽  
Author(s):  
Mitsuo Oshimura ◽  
Hiroyuki Kugoh ◽  
Minoru Koi ◽  
Motoyuki Shimizu ◽  
Hideto Yamada ◽  
...  

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