Nature Genetics
17, 32 - 39 (1997)
doi:10.1038/ng0997-32
DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3−26.1 is deleted in malignant brain tumoursJan Mollenhauer1, Stefan Wiemann1, Wolfram Scheurlen2, Bernhard Korn1, Yutaka Hayashi3, Klaus K. Wilgenbus1, *, Andreas von Deimling3
& Annemarie Poustka1
1Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
2Children's Hospital, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
3Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany.
*Current address: Bender & Co. GmbH, Dr. Boehringer Gasse5-11, A-1121 Vienna, Austria. Loss of sequences from human chromosome 10q has been associated with the progression of human cancer. Medulloblastoma and glioblastoma multiforme are the most common malignant brain tumours in children and adults, respectively. In glioblastoma multiforme, the most aggressive form, 80% of the tumours show loss of 10q. We have used representational difference analysis to identify a homozygous deletion at 10q25.3−26.1 in a medulloblastoma cell line and have cloned a novel gene, DMBT1, spanning this deletion. DMBT1 shows homology to the scavenger receptor cysteine-rich (SRCR) superfamily. Intragenic homozygous deletions have been detected in 2/20 medulloblastomas and in 9/39 glioblastomas multiformes. Lack of DMBT1 expression has been demonstrated in 4/5 brain-tumour cell lines. We suggest that DMBT1 is a putative tumour-suppressor gene implicated in the carcinogenesis of medulloblastoma and glioblastoma multiforme.
REFERENCES
- Albarosa, R. et al. Deletion mapping of gliomas suggests the presence of two small regions for candidate tumor-suppressor genes in a 17-cM interval on chromosome 10q. Am. J. Hum. Genet. 58, 1260−1267 (1996). | PubMed | ISI | ChemPort |
- Rasheed, A. et al. Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25. Oncogene 10, 2243−2246 (1995). | PubMed | ISI | ChemPort |
- Herbst, R., Weiss, J., Ehnis, A., Cavenee, W.K. & Arden, K.C. Loss of heterozygosity for 10q22-10qter in malignant melanoma progression. Cancer Res. 54, 3111−3114 (1994). | PubMed | ISI | ChemPort |
- Peiffer, S.L. et al. Allelic loss of sequences from the long arm of chromosome 10 and replication errors in endometrial cancers. Cancer Res. 55, 1922−1926 (1995). | PubMed | ISI | ChemPort |
- Zedenius, J. et al. Deletions of the long arm of chromosome 10 in progression of follicular thyroid tumors. Hum. Genet. 97, 299−303 (1996). | PubMed | ChemPort |
- Hahn, S.A. et al. Allelotype of pancreatic adenocarcinoma using xenograft enrichment. Cancer Res. 55, 4670−4675 (1995). | PubMed | ISI | ChemPort |
- Gray, I.C. et al. Loss of the chromosomal region 10q23-25 in prostate cancer. Cancer Res. 55, 4800−4803 (1995). | PubMed | ISI | ChemPort |
- Kühl, J. et al. for the German Pediatric Brain Tumor Study Group. Preradiation chemotherapy of children with poor-prognosis medulloblastoma: response rate and toxicity of the ifosfamide-containing multidrug regimen HIT 88/89. Am. J. Pediatr. Hematol. Oncol. 15 (Suppl. A), 567−571 (1993).
- Neumann, E. et al. Cytogenetic analysis of 109 pediatric central nervous system tumors. Cancer Genet. Cytogenet. 71, 40−49 (1993). | Article | PubMed | ISI | ChemPort |
- Fujii, Y., Hongo, T. & Hayashi, Y. Chromosome analysis of brain tumors in childhood. Genes Chromosomes Cancer 11, 205−215 (1994). | PubMed | ChemPort |
- Schütz, B. et al. Mapping of chromosomal gains and losses in primitive neuroectodermal tumors by comparative genomic hybridization. Genes Chromosomes Cancer 16, 196−203 (1996). | Article | PubMed | ISI |
- Cogen, P., Daneshvar, L., Metzger, A. & Edwards, M. Deletion mapping of the medulloblastoma locus on chromosome 17p. Genomics 8, 279−285 (1990). | PubMed | ChemPort |
- Thomas, G. & Raffel, C. Loss of heterozygosity on 6q, 16q, and 17p in human central nervous system primitive neuroectodermal tumors. Cancer Res. 51, 639−643 (1991). | PubMed | ChemPort |
- Albrecht, S. et al. Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11p, and 17p in medulloblastomas. Neuropathol. Appl. Neurobiol. 20, 74−81 (1994). | PubMed | ChemPort |
- Scheurlen, W. et al. High resolution deletion mapping of chromosome 17p in childhood primitive neuroectodermal tumors (PNET) reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in band 17p11.2. Genes Chromosomes Cancer 18, 50−58 (1997). | Article | PubMed | ChemPort |
- Biegel, J.A. et al. Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system. Genes Chromosomes Cancer 1, 139−147 (1989). | PubMed | ChemPort |
- Biegel, J.A. et al. Isochromosome 17q demonstrated by interphase fluorescence in situ hybridization in primitive neuroectodermal tumors of the central nervous system. Genes Chromosomes Cancer 14, 85−96 (1995). | PubMed | ChemPort |
- Lang, F.F., Miller, D.C., Koslow, M. & Newcomb, E.W. Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J. Neurosurg. 81, 427−436 (1994). | PubMed | ISI | ChemPort |
- Steck, P.A. et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet. 15, 356−362 (1997). | Article | PubMed | ISI | ChemPort |
- Li, J. et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943−1947 (1997). | Article | PubMed | ISI | ChemPort |
- Lisitsyn, N., Lisitsyn, N. & Wigler, M. Cloning the differences between two complex genomes. Science 259, 946−951 (1993). | PubMed | ISI | ChemPort |
- Kelsell, D.P. et al. Development of a panel of monochromosomal somatic cell hybrids for rapid gene mapping. Ann. Hum. Genet. 59, 233−241 (1995). | PubMed | ISI |
- Chumakov, I.M. et al. A YAC contig map of the human genome. Nature 377 (Suppl.), 175−297 (1995). | PubMed | ISI | ChemPort |
- Ioannou, P. et al. A new bacteriophage P1-derived vector for the propagation of large human DNA fragments. Nature Genet. 6, 84−89 (1994). | Article | PubMed | ChemPort |
- Cheng, H., Bjerknes, M. & Chen, H. CRP-ductin: A gene expressed in intestinal crypts and in pancreatic and hepatic ducts. Anatom. Rec. 244, 327−343 (1996). | Article | ChemPort |
- Nunes, D.P., Keates, A.C., Afdhal, N.H. & Offner, G.D. Bovine gall-bladder mucin contains two distinct tandem repeating sequences: evidence for scavenger receptor cysteine-rich repeats. Biochem. J. 31, 41−48 (1995).
- Kozak, M. Analysis of 5' noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125−8148 (1987). | PubMed | ISI | ChemPort |
- Bork, P. & Beckmann, G. The CUB domain a widespread module in developmentally regulated proteins. J. Mol. Biol. 231, 539−545 (1993). | Article | PubMed | ISI | ChemPort |
- Bork, P. & Sander, C. A large domain common to sperm receptors (Zp2 and Zp3) and TGF-
 type III receptor. FEBS Lett. 300, 237−240 (1992). | Article | PubMed | ISI | ChemPort |
- Resnick, D., Pearson, A. & Krieger, M. The SRCR super-family: a family reminiscent of the Ig superfamily. Trends Biochem. Sci. 19, 5−8 (1994). | Article | PubMed | ISI | ChemPort |
- Li, X.J. & Snyder, S.H. Molecular cloning of ebnerin, a von Ebner's gland protein associated with taste buds. J. Biol. Chem. 270, 17674−17679 (1995). | Article | PubMed | ISI | ChemPort |
- Starling, G.C. et al. Characterization of mouse CD6 with novel monoclonal antibodies which enhance the allogeneic mixed leukocyte reaction. Eur. J. Immunol. 26, 738−746 (1996). | PubMed | ChemPort |
- Ullrich, A. et al. The secreted tumor-associated antigen 90K is a potent immune stimulator. J. Biol. Chem. 269, 18401−18407 (1994). | PubMed | ISI | ChemPort |
- Law, S.K.A. et al. A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. Eur. J. Immunol. 23, 2320−2325 (1993). | PubMed | ISI | ChemPort |
- al-Awqati, Q. Plasticity in epithelial polarity of renal intercalated cells: targeting of the H+-ATPase and band 3. Am. J. Physiol. 270, 1571−1580 (1996).
- Whitney, G.S. et al. The membrane-proximal scavenger receptor cysteine-rich domain of CD6 contains the activated leukocyte cell adhesion molecule binding site. J. Biol. Chem. 270, 18187−18190 (1995). | Article | PubMed | ChemPort |
- Petersen, I. et al. Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p. Br. J. Cancer 75, 79−86 (1997). | PubMed | ISI | ChemPort |
- Azizi, E. et al. Familial cutaneous malignant melanoma and tumors of the nervous system: a hereditary cancer syndrome. Cancer 76, 1571−1578 (1995). | PubMed | ChemPort |
- Kleihues, P., Burger, P.C. & Scheithauer, B.W. Histological Typing of Tumors of the Central Nervous System, 2nd ed. (Springer-Verlag, New York, 1993).
- Miller, S., Dykes, D. & Polesky, H. A simple salting out method for extracting DNA from human nucleated cells. Nucleic Acids Res. 16, 1215 (1988). | PubMed | ISI | ChemPort |
- Poustka, A. Physical mapping by PFGE. Methods 1, 204−211 (1990). | ChemPort |
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