Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

The novel human HALR gene encodes a protein homologous to the ALR (ALL-1-related) gene product, and maps to chromosome 7q36 associated with leukemia and developmental defects

VT Chow PhD, YC Tan BSc

Human Genome Laboratory, Dept Microbiology, National University of Singapore, Kent Ridge, Singapore,

AIMS: To identify and characterize the cDNA of a novel human gene (designated HALR for homologous to ALR) from the SiHa cervical carcinoma cell line. METHODS: RT-PCR, DNA sequencing and bioinformatics. RESULTS: Northern blotting of human fetal tissues revealed ~12-kb transcripts, while RT-PCR demonstrated that HALR is ubiquitously expressed in a wide range of human tissues and cancers. The HALR ORF encodes a large hydrophilic protein comprising >4,000 amino acids, with a calculated molecular mass of ~440 kD. HALR possesses a SET domain, a HMG box, three PHD-type zinc fingers, a leucine zipper-like pattern, two potential transactivating domains as well as several nuclear localization signals and nuclear receptor interaction motifs. The HALR protein exhibits significant similarity to the myeloid/lymphoid or mixed-lineage leukemia (MLL or ALL-1) and the ALL-1-related (ALR) human proteins, especially between their SET and PHD domains. ALR and ALL-1 are evolutionarily conserved and play roles in cellular differentiation. ALL-1 is also involved in chromosomal translocation or rearrangement found in acute leukemia. The HALR gene has been localized to chromosome 7q36, is estimated to span at least 90 kb, and contains >40 exons. Loss of chromosome 7 or deletions of its long arm are frequently encountered in leukemias, implying that this region may harbor potential tumor suppressor or transcriptional regulator genes whose loss of function contribute to leukemogenesis. Deletion of 7q is also associated with holoprosencephaly 3, a midline embryonic defect affecting forebrain development. CONCLUSIONS: These features suggest that HALR may be a transcription factor involved in neoplastic and/or developmental diseases.

KEY WORDS: SET domain, PHD zinc finger, transcription factor, holoprosencephaly 3.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic risk assessment.