Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors

Genomics. 2000 Jan 15;63(2):165-72. doi: 10.1006/geno.1999.6077.

Abstract

We previously defined a common region of 17q25 loss in breast and ovarian tumors, suggesting localization of at least one putative tumor suppressor gene. Genomic clones from the interval were used to isolate candidate transcripts. One novel transcript had strong homology to a septin family of GTPase genes involved in cytokinesis. This gene was recently identified as a myeloid/lymphoid leukemia (MLL) fusion protein partner in acute myeloid leukemia and was named MSF (MLL septin-like fusion). As this gene may play roles in both leukemogenesis and tumorigenesis, it is essential to understand its structure and normal expression. We cloned two human alternative transcripts and identified a third database variant of MSF. RNA expression studies with a probe common to the three novel sequences showed differential expression of 4.0- and 3.0-kb transcripts in all adult and fetal tissues tested. A probe spanning sequence unique to one MSF variant detected specific expression of the 4.0-kb transcript in all tissues. Another probe unique to a different MSF variant detected a 4.0-kb transcript only in skeletal muscle. Proteins of 422 and 586 amino acids were predicted from the novel alternate transcripts and included both a xylose isomerase 1 domain and a GTPase domain. Nine common exons, three alternatively spliced exons, and six polymorphisms were identified.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17 / genetics*
  • Cloning, Molecular
  • DNA Primers / genetics
  • Exons
  • Female
  • GTP Phosphohydrolases*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Gene Expression
  • Genes, Tumor Suppressor
  • Humans
  • Introns
  • Molecular Sequence Data
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Genetic
  • Septins
  • Sequence Homology, Amino Acid

Substances

  • DNA Primers
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • SEPTIN9 protein, human
  • Septins

Associated data

  • GENBANK/AF189712
  • GENBANK/AF189713