Constitutional alterations of the ATM gene in early onset sporadic breast cancer

• Published in: Journal of medical genetics Vol. 39; no. 10; pp. 751 - 753
• Main Authors: Maillet, P, Bonnefoi, H, Vaudan-Vutskits, G, Pajk, B, Cufer, T, Foulkes, W D, Chappuis, P O, Sappino, A-P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.10.2002; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Age; Ataxia; Ataxia Telangiectasia - genetics; Ataxia Telangiectasia Mutated Proteins; ATM mutations; Biological and medical sciences; Blood & organ donations; Breast cancer; Breast Neoplasms - genetics; Cell Cycle Proteins; Confidence intervals; Deoxyribonucleic acid; DNA; DNA-Binding Proteins; early onset breast cancer; Female; Genetic Testing; Gynecology. Andrology. Obstetrics; Humans; Kinases; Letter to JMG; Mammary gland diseases; Medical sciences; Middle Aged; Mutation; Polymorphism, Genetic - genetics; Precancerous Conditions - genetics; Protein-Serine-Threonine Kinases - genetics; Tumor Suppressor Proteins; Tumors; Womens health; Human; Sporadic; Pathogenesis; Malignant tumor; Chromosome C11; Genetic determinism; Mammary gland diseases; Gene; Risk factor; Early; Mammary gland; Mutation; Locus
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.39.10.751

After initial denaturation at 94°C for five minutes, each of the 35 cycles of amplification consisted of 30 seconds at 94°C, 30 seconds at optimal annealing temperature, 30 seconds at 72°C, followed by final extension of five minutes at 72°C. The oligonucleotide primer pairs used to amplify all the ATM coding exons have been described previously, with conditions for each pair. 19 Single strand conformation polymorphism (SSCP)/heteroduplex (HTX) analysis was performed as previously described. 20 Briefly, 10 [micro]l of PCR products containing 10 [micro]l non-denaturing loading buffer were boiled for five minutes, chilled on ice for 10 minutes, and loaded on a 6% MDE acrylamide gel (FMC Bioproducts, Rockland, ME, USA). The 11q23 locus encompassing the ATM gene is often deleted in breast carcinoma and reduction in the levels of ATM mRNA and protein has also been observed in this type of tumour. 24 In addition, somatic alterations of ATM have been reported in lymphoproliferative disorders. 22, 25, 26 Interestingly, by revealing missense mutations and complex intragenic rearrangements, the spectrum of somatic mutations found in these malignancies differs from that of classical AT patients, leading to the suggestion that there may exist two classes of ATM mutations, that is, the "null" mutations (complete/near complete loss of function) and the "impairing" mutations (reduced function).