Carcinogenesis, Vol. 20, No. 11, 2189-2192,
November 1999
© 1999 Oxford University Press
Short Communications |
A novel sensitive method to detect frameshift mutations in exonic repeat sequences of cancer-related genes
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 69372 Lyon Cedex 08, France
We have investigated frameshift mutations in exonic repeats in the ATR, BRCA1, BRCA2, PTCH, CTCF, Cx26, NuMa and TGFßRII genes, using human tumor samples from stomach, esophagus, breast and skin and melanoma, as well as colon cancer and endometrial cancer cell lines (125 samples in total). We developed a sensitive method to detect mutations in the repeats, using the introduction of an artificial restriction site into a repeat. The method detects a single mutant among 103 normal genes. Thus, an alteration in a repeated sequence can be detected unambiguously. The (A)8 repeat of BRCA2 was found mutated in only two of five colon cell lines with microsatellite instability (MI+). The ATR gene has an (A)10 repeat which was altered in two of three MI+ stomach cancer samples and one of three MI+ endometrial cell lines. The TGFßRII gene [with an (A)10 repeat] had the maximal frequency of mutations: 10 out of 13 MI+ samples. At least one sample from all types of cancers, except melanomas, was positive for TGFßRII gene mutations. No mutations were found in repeats in the BRCA1, PTCH, CTCF, NuMA and Cx26 genes in any types of tumors examined. In conclusion, our study indicates that repeats were altered only in MI+ cells and that the mutation frequencies in the genes studied differ among tumor types. Based on these results, we discuss meaningful and meaningless alterations in exonic repeats.
Abbreviations: HNPCC, human non-polyposis colorectal cancer; MI, microsatellite instability; RER, replication error.
1 To whom correspondence should be addressed Email: mironov{at}iarc.fr
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. A. Lewis, S. Mullany, B. Thomas, J. Chien, R. Loewen, V. Shridhar, and W. A. Cliby Heterozygous ATR Mutations in Mismatch Repair-Deficient Cancer Cells Have Functional Significance Cancer Res., August 15, 2005; 65(16): 7091 - 7095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Duval and R. Hamelin Mutations at Coding Repeat Sequences in Mismatch Repair-deficient Human Cancers: Toward a New Concept of Target Genes for Instability Cancer Res., May 1, 2002; 62(9): 2447 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mori, J. Yin, A. Rashid, B. A. Leggett, J. Young, L. Simms, P. M. Kuehl, P. Langenberg, S. J. Meltzer, and O. C. Stine Instabilotyping: Comprehensive Identification of Frameshift Mutations Caused by Coding Region Microsatellite Instability Cancer Res., August 1, 2001; 61(16): 6046 - 6049. [Abstract] [Full Text] [PDF]
|
|