title: No evidence for constitutional ATM mutation in breast/gastric cancer families.
abstract: Ataxia-Telangiectasia (A-T) is a rare autosomal recessive disease characterised by cutaneous telangiectasia, cerebellar ataxia, immunodeficiency, high sensitivity to ionising radiation, chromosomal instability and an increased risk of cancer. The gene mutated in A-T patients, ATM, is located on chromosome 11q22-23. ATM heterozygotes are thought to have a high tendency to develop malignancies, such as breast cancer. In order to determine the contribution of heterozygous ATM mutation to cancer, studies of cancer-affected patients have been undertaken in non site-specific cancer families and sporadic breast cancer cases. No evidence of an important role of ATM heterozygous mutations has been shown. In order to give another contribution to these results, we tried to define a specific family phenotype according to the most common cancers observed in ATM heterozygotes. Breast and gastric cancers appear to be the most frequent malignancies in A-T carriers and one ATM germ-line mutation has been described in a breast/gastric cancer family. Therefore we further investigated the role of ATM mutation in additional breast/gastric cancer families. In eighteen families associating these two malignancies, we used the protein transcription/translation test to detect ATM mutations in the index case from each family. We found one case of ATM mutation which did not cosegregate with the gastric cancer in the family.
authors.affiliation: Laboratoire d'Oncologie Moleculaire, INSERM CRI 9502 and EA2145, Centre Jean Perrin, BP 392, 63011 Clermont-Ferrand cedex 1, France.
authors.forename: J O
authors.initials: JO
authors.lastname: Bay
authors.forename: M
authors.initials: M
authors.lastname: Grancho
authors.forename: D
authors.initials: D
authors.lastname: Pernin
authors.forename: N
authors.initials: N
authors.lastname: Presneau
authors.forename: P
authors.initials: P
authors.lastname: Rio
authors.forename: A
authors.initials: A
authors.lastname: Tchirkov
authors.forename: N
authors.initials: N
authors.lastname: Uhrhammer
authors.forename: P
authors.initials: P
authors.lastname: Verrelle
authors.forename: R A
authors.initials: RA
authors.lastname: Gatti
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005190:Family; D005192:Family Health; D005220:Fathers; D005260:Female; D017353:Gene Deletion; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D019869:Phosphatidylinositol 3-Kinases