Involvement of the ALL-1 gene in a solid tumor.
Translocations involving chromosome band 11q23, found in 5-10% of human acute leukemias, disrupt the ALL-1 gene. This gene is fused by reciprocal translocation with a variety of other genes in acute lymphoblastic and myelogenous leukemias, and it undergoes self-fusion in acute myeloid leukemias with normal karyotype or trisomy 11. Here we report an alteration of the ALL-1 gene in a gastric carcinoma cell line (Mgc80-3). Characterization of this rearrangement revealed a three-way complex translocation, involving chromosomes 1 and 11, resulting in a partial duplication of the ALL-1 gene. Sequencing of reverse transcription-PCR products and Northern blot analysis showed that only the partially duplicated ALL-1 gene was transcribed, producing an mRNA with exon 8 fused to exon 2. This report of ALL-1 gene rearrangement in a solid tumor suggests that ALL-1 plays a role in the pathogenesis of some solid malignancies. The absence of the normal transcript in this cell line, in association with the loss-of-heterozygosity studies on chromosome 11q23 seen in solid tumors, suggests that ALL-1 is involved in tumorigenesis by a loss-of-function mechanism.
Baffa
R
R
Jefferson Cancer Institute, Jefferson Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Negrini
M
M
Schichman
S A
SA
Huebner
K
K
Croce
C M
CM
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D006822:Hybrid Cells; D007438:Introns; D007938:Leukemia / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D051788:Myeloid-Lymphoid Leukemia Protein; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D012377:Rodentia; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase