Loss of heterozygosity at the ATBF1-A locus located in the 16q22 minimal region in breast cancerReport as inadecuate




Loss of heterozygosity at the ATBF1-A locus located in the 16q22 minimal region in breast cancer - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 8:262

First Online: 16 September 2008Received: 01 May 2008Accepted: 16 September 2008DOI: 10.1186-1471-2407-8-262

Cite this article as: Kai, K., Zhang, Z., Yamashita, H. et al. BMC Cancer 2008 8: 262. doi:10.1186-1471-2407-8-262

Abstract

BackgroundLoss of heterozygosity LOH on the long arm of chromosome 16 is one of the most frequent genetic events in solid tumors. Recently, the AT-motif binding factor 1 ATBF1-A gene, which has been assigned to chromosome 16q22.3-23.1, was identified as a plausible candidate for tumor suppression in solid tumors due to its functional inhibition of cell proliferation and high mutation rate in prostate cancer. We previously reported that a reduction in ATBF1-A mRNA levels correlated with a worse prognosis in breast cancer. However, the mechanisms regulating the reduction of ATBF1-A mRNA levels such as mutation, methylation in the promoter region, or deletion spanning the coding region have not been fully examined. In addition, few studies have analyzed LOH status at the ATBF1-A locus, located in the 16q22 minimal region.

MethodsProfiles of ATBF1-A mRNA levels that we previously reported for 127 cases were used. In this study, breast cancer specimens as well as autologous blood samples were screened for LOH using 6 polymorphic microsatellite markers spanning chromosome band 16q22. For mutational analysis, we selected 12 cases and analyzed selected spots in the ATBF1-A coding region at which mutations have been frequently reported in prostate cancer.

ResultsForty-three cases that yielded clear profiles of LOH status at both D16S3106 and D16S3018 microsatellites, nearest to the location of the ATBF1-A gene, were regarded as informative and were classified into two groups: LOH 22 cases and retention of heterozygosity 21 cases. Comparative assessment of the ATBF1-A mRNA levels according to LOH status at the ATBF1-A locus demonstrated no relationship between them. In the 12 cases screened for mutational analysis, there were no somatic mutations with amino acid substitution or frameshift; however, two germ line alterations with possible polymorphisms were observed.

ConclusionThese findings imply that ATBF1-A mRNA levels are regulated at the transcriptional stage, but not by genetic mechanisms, deletions LOH, or mutations.

AbbreviationsLOHloss of heterozygosity

ATBF1-AAT-motif binding factor 1-A

TSGtumor suppressor gene

AFPalpha-fetoprotein

ROHretention of heterozygosity

NDnot determined

UIuninformative

SNPsingle nucleotide polymorphism

miRNAmicroRNA

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-8-262 contains supplementary material, which is available to authorized users.

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Author: Kazuharu Kai - Zhenhuan Zhang - Hiroko Yamashita - Yutaka Yamamoto - Yutaka Miura - Hirotaka Iwase

Source: https://link.springer.com/







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