A familial RB1 mutation detected by the HOT technique is homozygous in a second primary neoplasm

Oncogene. 1991 Dec;6(12):2353-6.


Using the hydroxylamine-osmium tetroxide (HOT) technique, we have identified a constitutional point mutation in the retinoblastoma susceptibility gene (RB1) which segregates with the expression of retinoblastoma in five affected family members. One member developed a second primary tumor, a small-cell lung carcinoma (SCLC), which metastasized to the liver. Analysis of liver tumour DNA revealed homozygosity for the constitutional mutation, a G----A transition at the fifth base of intron 21, resulting in the excision of exon 21 from the mRNA. This is the first demonstration of homozygotization of a constitutional RB mutation in a metastatic second primary tumour and underlines the usefulness of the HOT technique for identification of mutations of the RB1 gene.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Carcinoma, Small Cell / genetics*
  • Exons
  • Eye Neoplasms / genetics*
  • Female
  • Genes, Retinoblastoma*
  • Genetic Techniques
  • Homozygote*
  • Humans
  • Hydroxylamine
  • Hydroxylamines
  • Lung Neoplasms / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • Osmium Tetroxide
  • Pedigree
  • Polymerase Chain Reaction / methods
  • RNA Splicing
  • Repetitive Sequences, Nucleic Acid
  • Retinoblastoma / genetics*


  • Hydroxylamines
  • Oligodeoxyribonucleotides
  • Hydroxylamine
  • Osmium Tetroxide