Journal Article

A novel sensitive method to detect frameshift mutations in exonic repeat sequences of cancer-related genes

N. Mironov, L.A.M. Jansen, W.-B. Zhu, A.-M. Aguelon, G. Reguer and H. Yamasaki

in Carcinogenesis

Volume 20, issue 11, pages 2189-2192
Published in print November 1999 | ISSN: 0143-3334
Published online November 1999 | e-ISSN: 1460-2180 | DOI:
A novel sensitive method to detect frameshift mutations in exonic repeat sequences of cancer-related genes

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  • Clinical Cytogenetics and Molecular Genetics


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We have investigated frameshift mutations in exonic repeats in the ATR, BRCA1, BRCA2, PTCH, CTCF, Cx26, NuMa and TGFβRII 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 TGFβRII 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 TGFβRII 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.

Keywords: HNPCC, human non-polyposis colorectal cancer; MI, microsatellite instability; RER, replication error.

Journal Article.  3336 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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