p53 mosaicism with an exon 8 germline mutation in the founder of a cancer-prone pedigree.
Changes in the tumor-suppressor gene p53 are frequently acquired during the course of malignant development of human tumors. Recently, constitutional heterozygous mutations in p53 exon 7 have been identified as the primary cause of cancer predisposition in cases of the familial Li-Fraumeni cancer syndrome. These findings underline the need for extensive mutation screening in families with high cancer incidence. This report describes the detection and follow-up by two-dimensional single-strand conformation polymorphism analysis (2DSSCP) of a new germline mutation of p53 exon 8 in a case of suspected Li-Fraumeni syndrome. Although a high cancer incidence had been reported in the family history of the father of siblings suffering from brain tumor and rhabdomyosarcoma, a constitutional heterozygous p53 mutation was identified only in the affected children. Retrospective analysis of archival tissue of a half-sister who died several years ago from a tumor of previously uncertain diagnosis revealed the same mutation. The mutation had therefore occurred in the germ cells of the mother, who thus appears to be a mosaic. The cancer predisposition of the paternal ancestors must have been due to other factors.
Children's Cancer Research Institute, St Anna Kinderspital, Vienna, Austria.
H
H
Kovar
A
A
Auinger
G
G
Jug
T
T
Müller
K
K
Pillwein
D000293:Adolescent; D001483:Base Sequence; D005091:Exons; D005260:Female; D016158:Genes, p53; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length