title: MLL2, the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines.
abstract: 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.
authors.affiliation: CRC Department of Oncology and Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust-MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: S F
authors.initials: SF
authors.lastname: Chin
authors.forename: M
authors.initials: M
authors.lastname: Muleris
authors.forename: S J
authors.initials: SJ
authors.lastname: Batley
authors.forename: V P
authors.initials: VP
authors.lastname: Collins
authors.forename: L M
authors.initials: LM
authors.lastname: Wiedemann
authors.forename: S
authors.initials: S
authors.lastname: Aparicio
authors.forename: C
authors.initials: C
authors.lastname: Caldas
mesh_terms: 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
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors; C063460:Trl protein, Drosophila