Choroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread alon... more Choroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only few high fidelity mouse models of p53-deficient malignant CPTs are available. We show here that c-MYC overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. In compound mutant mice, overexpression of c-MYC in an immunodeficient background led to a decreased incidence of CPP and reduced tumour bulk. Finally, reduced tumour size was also observed upon T-cell depletion in CPP-bearing mice. Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.
When The History and Geography of Human Genes was first published in 1994 it was met with univers... more When The History and Geography of Human Genes was first published in 1994 it was met with universal admiration, being described by one reviewer as ' a crowning achievement, a compendium of a career's work, and a sourcebook for years to come ' (Weiss, 1995) and by another as the raspberry chocolate cake of human population genetics : ' rich, dense, uniformly high in quality, heterogeneous in subject matter and best enjoyed by repeatedly removing from the … bookshelf to take small bites ' (Diamond, 1994). However, this compelling volume was, in its first incarnation, over 1000 pages in length and cost £120 and was therefore a daunting purchase for all but the most dedicated anthropological geneticist. The new abridged edition (missing the tables and colour maps of global allele frequency distribution which comprised half the original volume) is considerably shorter, and at one-fifth the price, finally accessible to anyone interested in the genetic ancestry of our species. The unmodified text, co-authored by Luca Cavalli-Sforza and his long-time Italian collaborators Menozzi and Piazza, is an impressive overview of human population relationships at the genetic level, summarized and interpreted in the light of archaeology, linguistics, and biological anthropology. The sheer breadth of coverage is staggering, with a global consideration of gene frequency distributions being followed by chapters devoted separately to Africa, Asia, Europe, the Americas, and Oceania (largely Australia and New Guinea). The downside of such encyclopaedic coverage, of course, is some lack of depth. No doubt archaeologists and linguists familiar with specific geographic regions will find relevant descriptions oversimplified or superseded by more recent research. The presentation of the genetics is similarly limited, both by its reliance on a data set made up of only ' classical ' genetic markers (i.e. blood group, protein, and enzyme variants) rather than newer
A cloned 15 kb genomic fragment from the human alpha 1(I) collagen gene (COL1A1) has been used as... more A cloned 15 kb genomic fragment from the human alpha 1(I) collagen gene (COL1A1) has been used as a probe on restriction digests of DNA from human-mouse somatic cell hybrids. Positive results on hybrids containing chromosome 17 as their only karyotypically visible human material confirm the assignment of this gene to chromosome 17. Hybrids which contain fragments of chromosome 17 are used to confirm the localization to 17q21-qter.
Restriction fragment length polymorphism at the D8S8 locus is explained by the occurrence of at l... more Restriction fragment length polymorphism at the D8S8 locus is explained by the occurrence of at least two alternative alleles at two separate TaqI sites; TaqI-A allele frequencies 0.73 and 0.27 and TaqI-B allele frequencies 0.94 and 0.06. The D8S8 locus has been assigned to 8q13-21.1, near to the carbonic anhydrase (CA) gene cluster, by in situ hybridization to metaphase chromosomes using both tritium and immunofluorescently labelled probes. Linkage analysis using the CEPH family DNA panel indicates a close genetic linkage between D8S8 and CA3, with a lod score of +7.80 at theta = 0.05 in males.
The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of... more The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of which encodes the ribosomal protein L7a, has been localized by an analysis of somatic cell hybrids to the long arm of chromosome 9. By the use of in situ hybridization the Surfeit locus has been further mapped to 9q33-34.
A cDNA corresponding to the beta-subunit of the human fibronectin receptor (beta-FNR) was used as... more A cDNA corresponding to the beta-subunit of the human fibronectin receptor (beta-FNR) was used as a probe in Southern blot analysis of mouse/human somatic cell hybrid DNAs and in in situ hybridization to metaphase chromosomes. The beta-FNR cDNA detects sequences present on human chromosome 10 as well as recognizing homologous sequences in the genome of the mouse parent of the somatic cell hybrids. In situ hybridization refined the localization of human sequences reacting with the beta-FNR cDNA to 10p11.2. The A-1A5 monoclonal antibody which recognizes the beta-subunit of the fibronectin receptor on the cell surface was used to confirm that the sequences present on chromosome 10 correspond to those required for expression of beta-FNR.
The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to... more The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c-erbA2 to the chromosome region 3p21-pter.
Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation brea... more Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12-21.
Ann. Hum. Genet. (1982), 46, 337-347 Printed in Great Britain ... A monoclonal antibody recognizi... more Ann. Hum. Genet. (1982), 46, 337-347 Printed in Great Britain ... A monoclonal antibody recognizing a cell surface antigen coded for by a gene on human chromosome 17 ... BY Y. HAI, D. SHEER, L. HIORNS, RW KNOWLES" AND A. TUNNACLIFFE Imperial Cancer Research ...
The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a ... more The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a radiation hybrid mapping panel and FISH analysis on human metaphase chromosomes. PCR-based analysis of a single chromosome hybrid panel identified the presence of the CD83 gene on human chromosome 6 and subsequent analysis of the Genebridge4 radiation panel located the gene between AFMa192wg9 and AFMb322wd1 with a lod score of 9.2. Finally, using FISH analysis the CD83 gene was localized to chromosome 6 band p23.
Choroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread alon... more Choroid plexus tumours (CPTs) account for 2-5% of brain tumours in children. They can spread along the neuraxis and can recur after treatment. Little is known about the molecular mechanisms underlying their formation and only few high fidelity mouse models of p53-deficient malignant CPTs are available. We show here that c-MYC overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. In compound mutant mice, overexpression of c-MYC in an immunodeficient background led to a decreased incidence of CPP and reduced tumour bulk. Finally, reduced tumour size was also observed upon T-cell depletion in CPP-bearing mice. Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.
When The History and Geography of Human Genes was first published in 1994 it was met with univers... more When The History and Geography of Human Genes was first published in 1994 it was met with universal admiration, being described by one reviewer as ' a crowning achievement, a compendium of a career's work, and a sourcebook for years to come ' (Weiss, 1995) and by another as the raspberry chocolate cake of human population genetics : ' rich, dense, uniformly high in quality, heterogeneous in subject matter and best enjoyed by repeatedly removing from the … bookshelf to take small bites ' (Diamond, 1994). However, this compelling volume was, in its first incarnation, over 1000 pages in length and cost £120 and was therefore a daunting purchase for all but the most dedicated anthropological geneticist. The new abridged edition (missing the tables and colour maps of global allele frequency distribution which comprised half the original volume) is considerably shorter, and at one-fifth the price, finally accessible to anyone interested in the genetic ancestry of our species. The unmodified text, co-authored by Luca Cavalli-Sforza and his long-time Italian collaborators Menozzi and Piazza, is an impressive overview of human population relationships at the genetic level, summarized and interpreted in the light of archaeology, linguistics, and biological anthropology. The sheer breadth of coverage is staggering, with a global consideration of gene frequency distributions being followed by chapters devoted separately to Africa, Asia, Europe, the Americas, and Oceania (largely Australia and New Guinea). The downside of such encyclopaedic coverage, of course, is some lack of depth. No doubt archaeologists and linguists familiar with specific geographic regions will find relevant descriptions oversimplified or superseded by more recent research. The presentation of the genetics is similarly limited, both by its reliance on a data set made up of only ' classical ' genetic markers (i.e. blood group, protein, and enzyme variants) rather than newer
A cloned 15 kb genomic fragment from the human alpha 1(I) collagen gene (COL1A1) has been used as... more A cloned 15 kb genomic fragment from the human alpha 1(I) collagen gene (COL1A1) has been used as a probe on restriction digests of DNA from human-mouse somatic cell hybrids. Positive results on hybrids containing chromosome 17 as their only karyotypically visible human material confirm the assignment of this gene to chromosome 17. Hybrids which contain fragments of chromosome 17 are used to confirm the localization to 17q21-qter.
Restriction fragment length polymorphism at the D8S8 locus is explained by the occurrence of at l... more Restriction fragment length polymorphism at the D8S8 locus is explained by the occurrence of at least two alternative alleles at two separate TaqI sites; TaqI-A allele frequencies 0.73 and 0.27 and TaqI-B allele frequencies 0.94 and 0.06. The D8S8 locus has been assigned to 8q13-21.1, near to the carbonic anhydrase (CA) gene cluster, by in situ hybridization to metaphase chromosomes using both tritium and immunofluorescently labelled probes. Linkage analysis using the CEPH family DNA panel indicates a close genetic linkage between D8S8 and CA3, with a lod score of +7.80 at theta = 0.05 in males.
The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of... more The Surfeit gene cluster which contains at least four very tightly spaced unrelated genes, one of which encodes the ribosomal protein L7a, has been localized by an analysis of somatic cell hybrids to the long arm of chromosome 9. By the use of in situ hybridization the Surfeit locus has been further mapped to 9q33-34.
A cDNA corresponding to the beta-subunit of the human fibronectin receptor (beta-FNR) was used as... more A cDNA corresponding to the beta-subunit of the human fibronectin receptor (beta-FNR) was used as a probe in Southern blot analysis of mouse/human somatic cell hybrid DNAs and in in situ hybridization to metaphase chromosomes. The beta-FNR cDNA detects sequences present on human chromosome 10 as well as recognizing homologous sequences in the genome of the mouse parent of the somatic cell hybrids. In situ hybridization refined the localization of human sequences reacting with the beta-FNR cDNA to 10p11.2. The A-1A5 monoclonal antibody which recognizes the beta-subunit of the fibronectin receptor on the cell surface was used to confirm that the sequences present on chromosome 10 correspond to those required for expression of beta-FNR.
The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to... more The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c-erbA2 to the chromosome region 3p21-pter.
Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation brea... more Using in situ hybridization, c-erbA1 has been mapped immediately distal to the translocation breakpoint on chromosome 17 in fibroblasts with a karyotype 46,XX, t(15;17)(q22;q11). Previous work has shown that c-erbA1 is proximal to the translocation breakpoint on chromosome 17 in the t(15;17)(q22;q12-21) in acute promyelocytic leukaemia. The oncogene can therefore be localized to the region of chromosome 17 between the breakpoints in 17q11 and 17q12-21.
Ann. Hum. Genet. (1982), 46, 337-347 Printed in Great Britain ... A monoclonal antibody recognizi... more Ann. Hum. Genet. (1982), 46, 337-347 Printed in Great Britain ... A monoclonal antibody recognizing a cell surface antigen coded for by a gene on human chromosome 17 ... BY Y. HAI, D. SHEER, L. HIORNS, RW KNOWLES" AND A. TUNNACLIFFE Imperial Cancer Research ...
The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a ... more The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a radiation hybrid mapping panel and FISH analysis on human metaphase chromosomes. PCR-based analysis of a single chromosome hybrid panel identified the presence of the CD83 gene on human chromosome 6 and subsequent analysis of the Genebridge4 radiation panel located the gene between AFMa192wg9 and AFMb322wd1 with a lod score of 9.2. Finally, using FISH analysis the CD83 gene was localized to chromosome 6 band p23.
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