Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples.

Chromosome region 11p15.5 harbors unidentified genes involved in neoplasms and in the genetic disease Beckwith-Wiedemann syndrome. The genetic analysis of a 170-kb region at 11p15.5 between loci D11S601 and D11S679 resulted in the identification of six transcriptional units. Three genes, hNAP2, CDKN1C, and KVLQT1, are well characterized, whereas three genes are novel. The three additional genes were designated BWR1A, BWR1B, and BWR1C. Full-length cDNAs for these three genes were cloned and nucleotide sequences were determined. While our work was in progress, BWR1C cDNA was described as IPL [Qian, N., Franck, D., O'Keefe, D., Dao, D. , Zhao, L., Yuan, L., Wang, Q., Keating, M., Walsh, C. & Tycko, B. (1997) Hum. Mol. Genet. 6, 2021-2029]. The cloning and mapping of these genes together with the fine mapping of the three known genes indicates that the transcriptional map of this region is likely to be complete. Because this region frequently is altered in neoplasms and in the genetic disease Beckwith-Wiedemann syndrome, we carried out a mutational analysis in tumor cell lines and Beckwith-Wiedemann syndrome samples that resulted in the identification of genetic alterations in the BWR1A gene: an insertion that introduced a stop codon in the breast cancer cell line BT549 and a point mutation in the rhabdomyosarcoma cell line TE125-T. These results indicate that BWR1A may play a role in tumorigenesis.

[1]  B. Tycko,et al.  The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis. , 1997, Human molecular genetics.

[2]  C. Croce,et al.  GOK: a gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. , 1997, Cancer research.

[3]  A. Feinberg,et al.  Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements , 1997, Nature Genetics.

[4]  Y. Fukushima,et al.  An imprinted gene p57KIP2 is mutated in Beckwith–Wiedemann syndrome , 1996, Nature Genetics.

[5]  C. Park,et al.  A novel gene product that couples TCR signaling to Fas(CD95) expression in activation-induced cell death. , 1996, Immunity.

[6]  D. Gerhard,et al.  Localization of a tumor suppressor gene in 11p15.5 using the G401 Wilms' tumor assay. , 1996, Human molecular genetics.

[7]  M. Rugge,et al.  Loss of heterozygosity for chromosome 11 in adenocarcinoma of the stomach. , 1996, Cancer research.

[8]  A. Feinberg,et al.  Multiple genetic loci within 11p15 defined by Beckwith-Wiedemann syndrome rearrangement breakpoints and subchromosomal transferable fragments. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  G. Hampton,et al.  Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3. , 1995, Cancer research.

[10]  C. Junien,et al.  Seven megabase yeast artificial chromosome contig at region 11p15: identification of a yeast artificial chromosome spanning the breakpoint of a chromosomal translocation found in a case of Beckwith-Wiedemann syndrome. , 1995, Cancer research.

[11]  S. Tilghman,et al.  Disruption of imprinting caused by deletion of the H19 gene region in mice , 1995, Nature.

[12]  W. Gerald,et al.  Epigenetic lesions at the H19 locus in Wilms' tumour patients , 1994, Nature Genetics.

[13]  A. Feinberg,et al.  Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour , 1994, Nature Genetics.

[14]  G. Bepler,et al.  Three tumor-suppressor regions on chromosome 11p identified by high-resolution deletion mapping in human non-small-cell lung cancer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[15]  O. Wiestler,et al.  Microsatellite analysis of loss of heterozygosity on chromosomes 9q, 11 p and 17p in medulloblastomas , 1994, Neuropathology and applied neurobiology.

[16]  Benjamin Tycko,et al.  Tumour-suppressor activity of H19 RNA , 1993, Nature.

[17]  R. Weksberg,et al.  Disruption of insulin–like growth factor 2 imprinting in Beckwith–Wiedemann syndrome , 1993, Nature genetics.

[18]  A. Mannermaa,et al.  Refinement of regional loss of heterozygosity for chromosome 11p15.5 in human breast tumors. , 1993, Cancer research.

[19]  R. Lothe,et al.  Frequent loss of 11p13 and 11p15 loci in male germ cell tumours , 1993, Genes, chromosomes & cancer.

[20]  A. Feinberg,et al.  Relaxation of imprinted genes in human cancer , 1993, Nature.

[21]  A. Feinberg,et al.  Tumor cell growth arrest caused by subchromosomal transferable DNA fragments from chromosome 11 , 1993, Science.

[22]  A. Viel,et al.  Chromosomal localisation of two putative 11p oncosuppressor genes involved in human ovarian tumours. , 1992, British Journal of Cancer.

[23]  D. Fults,et al.  Chromosome 11p15 deletions in human malignant astrocytomas and primitive neuroectodermal tumors. , 1992, Genomics.

[24]  B. Birren,et al.  Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  M. Lovett,et al.  Direct selection: a method for the isolation of cDNAs encoded by large genomic regions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Weissman,et al.  cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[27]  B. Weissman,et al.  Suppression of tumorigenicity in Wilms tumor by the p15.5-p14 region of chromosome 11. , 1991, Science.

[28]  J. Willey,et al.  Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  C. Junien,et al.  Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[30]  W. Cavenee,et al.  Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. , 1989, American journal of human genetics.

[31]  A. Reeve,et al.  Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms' tumor cells , 1989, Molecular and cellular biology.

[32]  J. H. Lee,et al.  Allele loss at the c-Ha-ras1 locus in human ovarian cancer. , 1989, Cancer research.

[33]  W. Cavenee,et al.  Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping , 1987, Nature.

[34]  Iqbal Unnisa Ali,et al.  Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia , 1987 .

[35]  H. Sambrook.  Molecular cloning : a laboratory manual. Cold Spring Harbor, NY , 1989 .

[36]  P. Radice,et al.  Loss of heterozygosity in human germinal tumors. , 1989, Cytogenetics and cell genetics.

[37]  A. Feinberg,et al.  Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. , 1989, American journal of human genetics.

[38]  C. Rogler,et al.  Deletions in human chromosome arms 11p and 13q in primary hepatocellular carcinomas. , 1988, Cytogenetics and cell genetics.