Abstract
In mammals, one of the Mad homologues, Smad2, was reported to be a mediator of TGF-beta signaling, and was found mutated in some cases of colon and lung cancers. To extend the analysis of this gene, we previously investigated the genomic organization of the human Smad2 gene and defined the structure of 12 exons and flanking introns. In this study, we designed 11 sets of intron-based primers to examine the entire coding region of the Smad2 gene. By the PCR-SSCP method using these primers, we screened genomic DNA sequences of colorectal cancers for mutations of the Smad2 gene. Though there was no mutation within all exons of the Smad2 gene, two of 60 sporadic colorectal cancers displayed deletions in the polypyrimidine tract preceding exon 4. Deletions of this region were also detected in colon cancer cell lines, and were clustered within cells exhibiting microsatellite instability. Deletions in the polypyrimidine tract had various effects on pre-mRNA splicing, but had no effect on the splicing of the Smad2 gene in these cases. However, our data support the idea that the polypyrimidine tract in the splicing acceptor site is a target of mutations in mismatch repair-deficient tumors.
Citations
May 14, 2003·Cellular Signalling·Bo JiangJohn Barnard
Mar 12, 1999·Japanese Journal of Clinical Oncology·Y ShitaraE Tahara
Sep 12, 2003·The Cancer Journal·Wen XieMichael Reiss
Jul 27, 2002·Annual Review of Genomics and Human Genetics·William M Grady, Sanford D Markowitz
Feb 4, 2009·BMC Molecular Biology·Norimasa MiuraJunichi Hasegawa
Oct 31, 2008·BMC Cancer·Esther H LipsHans Morreau
Jan 20, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·T SjöblomS Souchelnytskyi
Aug 6, 2002·American Journal of Human Genetics·Nadia EhteshamDaniel H Cohn
Feb 16, 2006·Cancer Letters·Wanglong QiuGloria H Su
Sep 13, 2005·Gene·Michael Stock, Florian Otto
May 28, 2011·Clinical Science·Juan F SantibañezCarmelo Bernabeu
Nov 6, 2014·Oncology Reports·Sung Ung MoonJee Hyun Kim
Aug 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick Mehlen, Eric R Fearon
Mar 4, 2000·Oncogene·S TakakuraJ Yokota
Dec 3, 2003·Oncogene·Sang-Uk HanSeong-Jin Kim
Jan 27, 2004·Oncogene·Manabu WadaTsutomu Chiba
Feb 1, 2019·Journal of Cellular Biochemistry·Yangyang ShiLing Yin
Jan 5, 2002·Fukushima Journal of Medical Science·T Fukushima, S Takenoshita
Mar 30, 2000·International Journal of Cancer. Journal International Du Cancer·Y EjimaM S Sasaki
Jun 8, 2000·International Journal of Cancer. Journal International Du Cancer·S YazumiR Takahashi