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  • Oncogenomics
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Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35–1p36.1 in a region frequently altered in human tumour cells

Abstract

Alterations of the distal portion of the short arm of chromosome 1 (1p) are among the earliest abnormalities of human colorectal tumours. Recently, we have cloned the Aflatoxin B1 aldehyde reductase (AFAR) gene from a smallest region of overlapping deletion that is frequently (48%) hemizygously deleted in sporadic colorectal cancer. AFAR is expressed in a broad range of tissues. Its closely related rat protein is the major factor conferring resistance of rats towards aflatoxin B1–induced liver carcinogenesis. Here, we have identified cDNAs covering two additional human AFAR-related genes localized in close proximity to the previously described AFAR at 1p35–36. We have analysed their structure and tissue-related expression. One of them, AFAR3, carries a Selenocysteine-Insertion Element (SECIS)-like structure that during translation may recode an in-frame TGA-stop codon to a selenocysteine. Two additional AFAR-pseudogenes are localized at Xq25 and 1p12, respectively. AFAR exon sequences share an identity of DNA and amino acids of more than 78%. Also large blocks of intronic sequences can be up to 98.6% identical. Knowledge of the AFAR genes and their structure will be essential in genetic and functional studies, where discrimination of the genes and proteins is a prerequisite for evaluating their individual functions.

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Acknowledgements

The Genbank Nucleotide Sequence Database Accession Numbers are AJ277796, AJ278012, AJ271883, AJ271800, AJ271801, AJ278012.

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Correspondence to Manfred Schwab.

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This study was supported by the Dr Mildred Scheel Stiftung.

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Praml, C., Savelyeva, L. & Schwab, M. Aflatoxin B1 aldehyde reductase (AFAR) genes cluster at 1p35–1p36.1 in a region frequently altered in human tumour cells. Oncogene 22, 4765–4773 (2003). https://doi.org/10.1038/sj.onc.1206684

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