255 467

Cited 44 times in

Forerunner genes contiguous to RB1 contribute to the development of in situ neoplasia

Authors
 Sangkyou Lee  ;  Joon Jeong  ;  Bogdan Czerniak  ;  William F. Benedict  ;  Jean-Pierre Issa  ;  Menashe Bar-Eli  ;  David McConkey  ;  Slawomir Filipek  ;  Xifeng Wu  ;  Philippe Spiess  ;  Susmita Samanta  ;  Saira S. Ahmed  ;  Jolanta Bondaruk  ;  Lanlan Shen  ;  Jain-Hua Zhou  ;  Herbert Barton Grossman  ;  Keith Baggerly  ;  Kuang S. Tang  ;  Tomasz Tuziak  ;  Mi-Sook Kim  ;  Steven E. Scherer  ;  Tadeusz Majewski 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.104(34) : 13732-13737, 2007 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2007
Abstract
We used human bladder cancer as a model system and the whole-organ histologic and genetic mapping strategy to identify clonal genetic hits associated with growth advantage, tracking the evolution of bladder cancer from intraurothelial precursor lesions. Six putative chromosomal regions critical for clonal expansion of intraurothelial neoplasia and development of bladder cancer were identified by using this approach. Focusing on one of the regions, which includes the model tumor suppressor RB1, we performed allelotyping of single-nucleotide polymorphic sites and identified a 1.34-Mb segment around RB1 characterized by a loss of polymorphism associated with the initial expansion of in situ neoplasia. This segment contains several positional candidate genes referred to by us as forerunner genes that may contribute to such expansion. We subsequently concentrated our efforts on the two neighbor genes flanking RB1, namely ITM2B and CHC1L, as well as P2RY5, which is located inside RB1. Here, we report that ITM2B and P2RY5 modulated cell survival and were silenced by methylation or point mutations, respectively, and thus by functional loss may contribute to the growth advantage of neoplasia. We also show that homozygous inactivation of P2RY5 was antecedent to the loss of RB1 during tumor development, and that nucleotide substitutions in P2RY5 represent a cancer predisposing factor.
Files in This Item:
T200700340.pdf Download
DOI
10.1073/pnas.0701771104
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Jeong, Joon(정준) ORCID logo https://orcid.org/0000-0003-0397-0005
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/97315
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links