Expression of recessive alleles by chromosomal mechanisms in retinoblastoma

  title={Expression of recessive alleles by chromosomal mechanisms in retinoblastoma},
  author={Webster K. Cavenee and T. P. Dryja and Robert A. Phillips and William F. Benedict and Roseline Godbout and Brenda L. Gallie and A. Linn Murphree and Louise C. Strong and R. White},
Inheritance of a mutation at the Rb-1 locus, which has been mapped to band q14 of human chromosome 13, results in predisposition to retinoblastoma. Cloned DNA segments homologous to arbitrary loci of human chromosome 13 and which reveal polymorphic restriction endonuclease recognition sequences, have been used to look for somatic genetic events that might occur during tumorigenesis. A comparison of constitutional and tumour genotypes from several cases indicates that tumorigenesis may result… 

Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour

Results of similar studies of another embryonal neoplasm, Wilms' tumour of the kidney, show that five cases were consistent with the presence on human chromosome 11 of a locus in which recessive mutational events are expressed after abnormal chromosomal segregation events during mitosis.

Genetic origin of mutations predisposing to retinoblastoma.

A new approach for identifying recessive mutant genes that lead to cancer and a conceptual basis for accurate prenatal predictions of cancer predisposition are suggested.

A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

The isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus is described, which is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas.

Genetics and cytogenetics of retinoblastoma.

  • B. Horsthemke
  • Medicine, Biology
    Cancer genetics and cytogenetics
  • 1992

Somatic events unmask recessive cancer genes to initiate malignancy

A study of retinoblastoma and Wilms' tumor in comparison to the normal constitutional cells of the patients, using enzyme and DNA markers near the predisposing genes, has shown that these genes are recessive to normal wild‐type alleles at the cellular level.

Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia

The results presented here demonstrate a loss of heterozygosity of several genes on chromosome 11 in primary breast tumors, and restriction fragment length polymorphism analysis of these DNAs suggests that the most frequent loss of sequences in breast tumors occurs between the beta-globin and parathyroid hormone loci on the short arm of chromosome 11.

Constitutional deletions predisposing to retinoblastoma

Patients with the heritable form of retinoblastoma carry a constitutional mutation in the retinOBlastoma locus in heterozygous form, which is identified in 3 out of 66 investigated unrelated gene carriers, using Southern blot analysis and Rb-gene cDNA-probes.



Familial retinoblastoma and chromosome 13 deletion transmitted via an insertional translocation.

Findings indicate that predisposition to retinoblastoma may be attributed to the loss of specific genetic material and that a chromosomal mechanism may explain apparent lack of gene penetrance in certain families.

Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma

It is tentatively concluded that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinOBlastoma (RB) locus.

Gene for hereditary retinoblastoma assigned to human chromosome 13 by linkage to esterase D.

Results assign the gene for the hereditary form of retinoblastoma to band q14 on chromosome 13, the same region which is affected in the chromosome deletion form of this eye tumor, and therefore suggest a common underlying mechanism in the pathogenesis of these two forms of retInoblastomas.

Regional assignment of genes for human esterase D and retinoblastoma to chromosome band 13q14.

The expression of human esterase D was evaluated quantitatively and qualitatively in five persons with partial deletions or duplications of chromosome 13 and showed that the locus of this enzyme is at band 13q14, which should aid in the diagnosis and genetic counseling of retinoblastoma.

Chromosomal deletion and retinoblastoma.

A new case of a deletion of the long arm of chromosome 13 is reported and its relation to previously reported cases is considered and the relation between the two genetic groups is considered.

Patient with 13 chromosome deletion: evidence that the retinoblastoma gene is a recessive cancer gene.

The data from this patient show that there is a total loss of genetic information at the location of the retinoblastoma gene within the tumor, and imply that recessive genes may play an important role in the development of certain human tumors including retin Oblastoma.

A chromosomal hypothesis of oncogenesis.

Pleiotropic effects of the gene for retinoblastoma

The findings indicate a pleiotropic effect of the retinoblastoma gene which may act as an initiator in two forms of neoplasia.

Chromosome segregation is frequently associated with the expression of recessive mutations in mouse cells.

  • E. EvesR. Farber
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1981
The results suggest that the expression of an autosomal recessive mutation in near-diploid mouse cells is frequently associated with events that result in the segregation of a physically linked marker and part or all of a chromosome.