No alterations in exon 21 of the RBI gene in sarcomas and carcinomas of the breast, colon, and lung

Studies of mutant genotypes of the retinoblastoma susceptibility gene (RBI) in different solid tumors have mainly been concentrated on the demonstration of loss of heterozygosity (LOH) at both internal and external polymorphic sites. One reason for this is the complex organization of the gene. The p105RB protein has been shown to interact with both DNA and regulatory cellular proteins and oncoproteins. The amino acids encoded by exon 21 are implicated in several of these interactions. Both point mutations and intragenic deletions involving exon 21 have previously been reported in human tumors. We have examined RBI exon 21 from a number of human tumor types where significant LOH in or around the RBI gene has been reported. DNA from 78 primary tumors was amplified using the polymerase chain reaction (PCR) with primers covering exon 21, followed by constant denaturant gel electrophoresis (CDGE). The 78 tumors included 11 breast carcinomas, 30 nonsmall cell lung carcinomas, 6 colon carcinomas, and 31 sarcomas. The small cell lung cancer cell line NCI‐H209, previously shown to harbour a point mutation in codon 706: TGT‐ > TTT (Cys‐ > Phe), was detected using CDGE. Apart from this control mutant cell line, we did not detect any mutations in the examined region in any of the tumors.

[1]  E. Hovig,et al.  Screening for mutations in human HPRT cDNA using the polymerase chain reaction (PCR) in combination with constant denaturant gel electrophoresis (CDGE). , 1992, Mutation research.

[2]  Thierry Soussi,et al.  TP53 tumor suppressor gene: A model for investigating human mutagenesis , 1992, Genes, chromosomes & cancer.

[3]  S. Friend,et al.  Constant denaturant gel electrophoresis as a rapid screening technique for p53 mutations. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[4]  T. L. McGee,et al.  Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene , 1991, Nature.

[5]  A. Rustgi,et al.  Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product , 1991, Nature.

[6]  Pearl S Huang,et al.  Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product , 1991, Nature.

[7]  T. Hunt,et al.  Cyclin A and the retinoblastoma gene product complex with a common transcription factor , 1991, Nature.

[8]  K. Münger,et al.  The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  W. Kaelin,et al.  The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein , 1991, Cell.

[10]  Joseph R. Nevins,et al.  The E2F transcription factor is a cellular target for the RB protein , 1991, Cell.

[11]  R. Weinmann,et al.  The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F , 1991, Cell.

[12]  N. L. Thangue,et al.  Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor , 1991, Nature.

[13]  T. Dryja,et al.  Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. , 1991, American journal of human genetics.

[14]  G E Moore,et al.  Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas. , 1991, Cancer research.

[15]  W. Benedict,et al.  Characterization of intragenic deletions in two sporadic germinal mutation cases of retinoblastoma resulting in abnormal gene expression. , 1991, Oncogene.

[16]  A. Tanigami,et al.  Allelotype of breast cancer: cumulative allele losses promote tumor progression in primary breast cancer. , 1990, Cancer research.

[17]  A. Okamoto,et al.  Variable mutations of the RB gene in small-cell lung carcinoma. , 1990, Oncogene.

[18]  W. Lee,et al.  Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[19]  F. Kaye,et al.  A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[20]  N. Dyson,et al.  The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations. , 1990, The EMBO journal.

[21]  R. Weinberg,et al.  Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[22]  W. Lee,et al.  Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. , 1990, Science.

[23]  E. Buckley,et al.  Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. , 1989, The New England journal of medicine.

[24]  K. Münger,et al.  Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. , 1989, The EMBO journal.

[25]  B. Gallie,et al.  Mutations in the RB1 gene and their effects on transcription , 1989, Molecular and cellular biology.

[26]  T. Dryja,et al.  Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. , 1989, American journal of human genetics.

[27]  Phang-lang Chen,et al.  Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation , 1989, Cell.

[28]  T. L. McGee,et al.  Structure and partial genomic sequence of the human retinoblastoma susceptibility gene. , 1989, Gene.

[29]  Lee Wh,et al.  Studies of the retinoblastoma gene in human sarcomas. , 1989 .

[30]  T. Dryja,et al.  Short, direct repeats at the breakpoints of deletions of the retinoblastoma gene. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[31]  W. J. Brammar,et al.  The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours. , 1989, Oncogene.

[32]  R. Weinberg,et al.  Point mutational inactivation of the retinoblastoma antioncogene. , 1989, Science.

[33]  J. Minna,et al.  Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. , 1988, Science.

[34]  Wen-Hwa Lee,et al.  SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene , 1988, Cell.

[35]  Stephen H. Friend,et al.  Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product , 1988, Nature.

[36]  A. Craft,et al.  Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. , 1988, The New England journal of medicine.

[37]  R. Weinberg,et al.  Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Wen-Hwa Lee,et al.  The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity , 1987, Nature.

[39]  W. Benedict,et al.  Complete or partial homozygosity of chromosome 13 in primary retinoblastoma. , 1987, Cancer research.

[40]  S. Hinrichs,et al.  Structural evidence for the authenticity of the human retinoblastoma gene. , 1987, Science.

[41]  W. Cavenee,et al.  Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Stephen H. Friend,et al.  A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma , 1986, Nature.

[43]  R. Myers,et al.  Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis. , 1985, Nucleic acids research.

[44]  Raymond L. White,et al.  Homozygosity of chromosome 13 in retinoblastoma. , 1984, The New England journal of medicine.

[45]  Yusaku Tagashira,et al.  Stabilities of nearest‐neighbor doublets in double‐helical DNA determined by fitting calculated melting profiles to observed profiles , 1981 .

[46]  D. Poland,et al.  Recursion relation generation of probability profiles for specific‐sequence macromolecules with long‐range correlations , 1974, Biopolymers.

[47]  A. Knudson.  Mutation and cancer: statistical study of retinoblastoma. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[48]  A. Brøgger,et al.  Constant denaturant gel electrophoresis, a modification of denaturing gradient gel electrophoresis, in mutation detection. , 1991, Mutation research.

[49]  V. Sheffield,et al.  Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[50]  L. Lerman,et al.  Sequence-determined DNA separations. , 1984, Annual review of biophysics and bioengineering.