The SRCR/SID region of DMBT1 defines a complex multi‐allele system representing the major basis for its variability in cancer

• DOI: 10.1002/gcc.10115
• Publication Date: 2002-10-09T04:27:15Z
• Authors: Jan Mollenhauer; Hanna Müller; Gaby Kollender; Stefan Lyer; Laura Diedrichs; Burkhard Helmke; Uffe Holmskov; Toon Ligtenberg; Stephan Herbertz; Inge Krebs; Jens Madsen; Floris Bikker; Liane Schmitt; Stefan Wiemann; Wolfram Scheurlen; Herwart F. Otto; Andreas von Deimling; Annemarie Poustka
• Keywords: Male; 0301 basic medicine; Lung Neoplasms; Scavenger Receptors; DNA Mutational Analysis; Variation (Genetics); Loss of Heterozygosity; Breast Neoplasms; Minisatellite Repeats; Scavenger; 03 medical and health sciences; Immunologic; Neoplasms; Receptors; Tumor Cells, Cultured; Humans; Point Mutation; Receptors, Immunologic; Lipoprotein; Alleles; Receptors, Lipoprotein; Receptors, Scavenger; Cultured; Brain Neoplasms; Genetic Variation; Membrane Proteins; Prostatic Neoplasms; DNA; DNA, Neoplasm; Exons; Scavenger Receptors, Class B; 3. Good health; Tumor Cells; Endometrial Neoplasms; Pancreatic Neoplasms; Neoplasm; Female; Class B

Abstract Deleted in malignant brain tumors 1 ( DMBT1 ) at 10q25.3–q26.1 has been proposed as a candidate tumor‐suppressor gene for and epithelial cancer. encodes multifunctional mucin‐like protein presumably involved differentiation protection. The consists of highly homologous repeating exon intron sequences. This specifically applies to the region coding repetitive scavenger receptor cysteine‐rich (SRCR) domains SRCR‐interspersed (SIDs) that constitutes major part gene. particular structure may previously have interfered with delineation alterations Uncovering these, however, is mechanistic importance. By combined approach, we conducted detailed mutational analysis, starting from panel 51 tumors, including 46 tumor cell lines five primary tumors. Alterations were present 22/31 (71%) investigated detail. Six showed de novo mutations, among these three point mutations combination loss heterozygosity. However, none unambiguously would be predicted lead an inactivation . We define seven distinct alleles based on variable numbers tandem repeats (VNTRs). At least 11 exclusively harbored VNTRs. data suggest SRCR/SID defines complex multi‐allele system escaped previous analyses represents basis variability thus compares mucins rather than conventional suppressors. © 2002 Wiley‐Liss, Inc.