Aflatoxin B sub(1) aldehyde reductase (AFAR) genes cluster at 1p35-1p36.1 in a region frequently altered in human tumour cells

• Published in: Oncogene Vol. 22; no. 30; pp. 4765 - 4773
• Main Authors: Praml, C, Savelyeva, L, Schwab, M
• Format: Journal Article
• Language: English
• Published: 24.07.2003
• ISSN: 0950-9232
• DOI: 10.1038/sj.onc.1206684

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 B sub(1) 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 B sub(1)-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-pseudo-genes 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.