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      DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours.

      Nature genetics
      Adult, Agglutinins, Amino Acid Sequence, Base Sequence, Brain Neoplasms, genetics, Cerebellar Neoplasms, Child, Chromosome Mapping, Chromosomes, Human, Pair 10, Cloning, Molecular, Conserved Sequence, DNA Primers, Gene Deletion, Glioblastoma, Homozygote, Humans, Medulloblastoma, Membrane Proteins, Molecular Sequence Data, Multigene Family, Polymerase Chain Reaction, Receptors, Cell Surface, biosynthesis, chemistry, Receptors, Immunologic, Receptors, Lipoprotein, Receptors, Scavenger, Recombinant Proteins, Scavenger Receptors, Class B, Sequence Alignment, Sequence Homology, Amino Acid

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          Abstract

          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 has 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 glibolastoma multiforme.

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          The CUB domain. A widespread module in developmentally regulated proteins.

          Sequence analysis has revealed the presence of 31 copies of an extracellular domain, here called CUB, in 16 functionally diverse proteins such as the dorso-ventral patterning protein tolloid, bone morphogenetic protein 1, a family of spermadhesins, complement subcomponents Cls/Clr and the neuronal recognition molecule A5. Most of them are known to be involved in developmental processes. Our analysis of this new family includes the identification of seven previously undescribed members, the characterization of conserved features and a topology prediction of this approximately 110 residue spanning domain, which suggests an antiparallel beta-barrel similar to those in immunoglobulins.
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            A new bacteriophage P1-derived vector for the propagation of large human DNA fragments.

            We have designed a P1 vector (pCYPAC-1) for the introduction of recombinant DNA into E. coli using electroporation procedures. The new cloning system, P1-derived artificial chromosomes (PACs), was used to establish an initial 15,000 clone library with an average insert size of 130-150 kilobase pairs (kb). No chimaerism has been observed in 34 clones, by fluorescence in situ hybridization. Similarly, no insert instability has been observed after extended culturing, for 20 clones. We conclude that the PAC cloning system will be useful in the mapping and detailed analysis of complex genomes.
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              A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily.

              The antibodies Ki-M8, Ber-Mac3, GHI/61 and SM4 define a human macrophage-associated antigen with a relative molecular mass of 130,000 which we designate M130. The protein was purified by immunoaffinity chromatography and an N-terminal and three internal amino acid sequences were obtained. A cDNA fragment was initially obtained by polymerase chain reaction (PCR) using reverse-translated primers. Several variant cDNA clones, derived from alternative spliced messages, were obtained from a lipopolysaccharide-stimulated human monocyte library and were sequenced. The relative abundance of these variants was evaluated by a series of overlapping PCR reactions. The size of the most representative cDNA is 3.7 kb and closely agrees with the mRNA size of 3.8 kb determined by Northern blot analysis. The membrane protein encoded contains a leader peptide of 40 residues, a putative extracellular domain of 1003 residues, followed by a hydrophobic segment of 24 residues and a cytoplasmic domain of 49 residues. The extracellular domain was found to contain nine repeating elements, of about 110 residues, which are similar to those of the scavenger receptor superfamily.
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