Cancer susceptibility in ataxia-telangiectasia.
Ataxia-telangiectasia (A-T) is a syndrome that has an extremely high incidence of cancer. Patients with the disease are homozygous for a mutant gene, the A-T gene, located at 11q23. Of these individuals, 30-40% develop cancer. Of these cancers, 80% are lymphoid. Those heterozygous for the A-T gene also have an increased frequency of cancer, the most notable being the 6.8-fold increase of breast cancer in females carriers. The syndrome is characterized cytogenetically by increased nonrandom chromosome breaks and rearrangements in lymphocytes involving the sites of the immunoglobulin and T-cell receptor genes. Clones of cells having the same rearrangements are often present in the blood of the A-T patients and if the rearrangements involve certain sites, especially a locus within 14q32, the propensity to progress to a malignant transformation is great. Sequencing the A-T gene and ascertaining its function should contribute significantly to our understanding of the molecular mechanisms underlying cancer susceptibility.
Peterson
R D
RD
Department of Pathology, University of South Alabama College of Medicine, Mobile.
Funkhouser
J D
JD
Tuck-Muller
C M
CM
Gatti
R A
RA
D001260:Ataxia Telangiectasia / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007938:Leukemia / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*