MLL2, the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines.
The Mixed Lineage Leukemia (MLL) gene is commonly involved in translocations in infantile leukemia and is amplified in some cases of adult myeloid leukemia. A homolog of MLL denoted MLL2, which represents the second human homolog of the Drosophila trithorax gene, was characterized by assembling ESTs, the KIAA0304 cDNA clone, RT - PCR fragments and a new clone isolated from a cDNA phage library and compared to the available genomic sequence. The MLL2 gene maps to 19q13.1, a region of frequent rearrangement or amplification in solid tumors. MLL2 consists of an 8.5 - 9 kb transcript and spans 20 kb of genomic DNA. The predicted MLL2 protein possesses all of the major domains defined in MLL and the two genes have a similar genomic structure. We find that MLL2 is amplified in two of 14 pancreatic carcinoma cell lines and one of five glioblastoma cell lines and is a likely critical gene in 19q13.1 amplifications. It is also a candidate for chromosomal rearrangements involving this chromosome locus. MLL2 is one additional mammalian trithorax-group gene with involvement in human cancer.
Huntsman
D G
DG
CRC Department of Oncology and Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust-MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
Chin
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SF
Muleris
M
M
Batley
S J
SJ
Collins
V P
VP
Wiedemann
L M
LM
Aparicio
S
S
Caldas
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C
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005091:Exons; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; C063460:Trl protein, Drosophila