Loss of heterozygosity at the ATBF1-A locus located in the 16q22 minimal region in breast cancer.
BACKGROUND
Loss 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.


METHODS
Profiles 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.


RESULTS
Forty-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.


CONCLUSIONS
These findings imply that ATBF1-A mRNA levels are regulated at the transcriptional stage, but not by genetic mechanisms, deletions (LOH), or mutations.
Kai
Kazuharu
K
Department of Breast and Endocrine Surgery, Faculty of Medical and Pharmaceutical Science, Kumamoto University, Kumamoto, Japan. kai-k@sc.itc.keio.ac.jp
Zhang
Zhenhuan
Z
Yamashita
Hiroko
H
Yamamoto
Yutaka
Y
Miura
Yutaka
Y
Iwase
Hirotaka
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002885:Chromosomes, Human, Pair 16; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000378:metabolism
D018398:Homeodomain Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C071660:ZFHX3 protein, human
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