title: A familial RB1 mutation detected by the HOT technique is homozygous in a second primary neoplasm.
abstract: 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.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: E
authors.initials: E
authors.lastname: Weir-Thompson
authors.forename: A
authors.initials: A
authors.lastname: Condie
authors.forename: R C
authors.initials: RC
authors.lastname: Leonard
authors.forename: J
authors.initials: J
authors.lastname: Prosser
mesh_terms: D000328:Adult; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics*; D005091:Exons; D005134:Eye Neoplasms / Q000235:genetics*; D005260:Female; D016161:Genes, Retinoblastoma; D005821:Genetic Techniques; D006720:Homozygote; D006801:Humans; D019811:Hydroxylamine; D006898:Hydroxylamines; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D009993:Osmium Tetroxide; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D012175:Retinoblastoma / Q000235:genetics*
chemical_list: D006898:Hydroxylamines; D009838:Oligodeoxyribonucleotides; D019811:Hydroxylamine; D009993:Osmium Tetroxide