✦ LIBER ✦

Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer

✍ Scribed by Louise Izatt; Jill Greenman; Shirley Hodgson; David Ellis; Sally Watts; Gillian Scott; Chris Jacobs; Rachael Liebmann; Marketa J. Zvelebil; Christopher Mathew; Ellen Solomon

Publisher: John Wiley and Sons
Year: 1999
Tongue: English
Weight: 263 KB
Volume: 26
Category: Article
ISSN: 1045-2257
DOI: 10.1002/(sici)1098-2264(199912)26:4<286::aid-gcc2>3.0.co;2-x

No coin nor oath required. For personal study only.

✦ Synopsis

Epidemiological studies have shown an increased risk of breast cancer in obligate ataxia telangiectasia (A-T) heterozygotes. We analyzed 100 samples from young breast cancer patients for mutations in ataxia-telangiectasia mutated (ATM), the gene responsible for the autosomal recessive condition, A-T, to determine whether A-T heterozygosity predisposes such individuals to develop breast cancer. These patients were selected from families with a moderate or absent family history of breast cancer and included a subset of 16 radiosensitive patients. Forty-four germline sequence variants were detected by fluorescent chemical cleavage of mismatch of RT-PCR products. These included seven rare variants found in nine patients (three described for the first time), but no truncating mutations. Although three variants were detected in the radiosensitive subset, this was not statistically significant compared to the nonradiosensitive group. One variant, G2765S, is likely to be a missense mutation, but the other six variants probably represent rare polymorphisms. However, five of the seven rare germline variants detected showed loss of heterozygosity of the wild-type ATM allele for one or more markers close to the ATM locus in matched tumor DNA. This high rate of somatic inactivation of ATM may indicate either that these rare variants play a role in breast cancer development or alternatively that a neighboring tumor suppressor gene is important for tumorigenesis. We found germline truncating ATM mutations to be rare in these young breast cancer patients and therefore they are unlikely to play a role in the etiology of their disease.

📜 SIMILAR VOLUMES

Identification of missense and truncatin

Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer

✍ Jill Greenman; Shehla Mohammed; David Ellis; Sally Watts; Gillian Scott; Louise 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 58 KB 👁 2 views

The cloning of the breast and ovarian cancer susceptibility gene, BRCA1, allows direct estimation of the proportion of these cancers in the general population which can be attributed to germline mutations in this gene. We have used a combination of SSCP, heteroduplex analysis, and chemical cleavage

Missense mutations of the PS-1/S182 gene

Missense mutations of the PS-1/S182 gene in german early-onset Alzheimer's disease patients

✍ Rupert Sandbrink; Dai Zhang; Konrad Beyreuther; Sibylle Schaeffer; Joachim Bauer 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 English ⚖ 231 KB 👁 2 views

Mutation analysis of the BRCA1 and BRCA2

Mutation analysis of the BRCA1 and BRCA2 genes results in the identification of novel and recurrent mutations in 6/16 Flemish families with breast and/or ovarian cancer but not in 12 sporadic patients with early-onset disease

✍ Kathleen Claes; Eva Machackova; Michel De Vos; Geert Mortier; Anne De Paepe; Lud 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 41 KB 👁 1 views

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within thi

Missense mutation in exon 11 (codon 378)

Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a French family with early-onset Alzheimer's disease and transmission study by mismatch enhanced allele specific amplification

✍ Roger Besançon; Alberta Lorenzi; Marc Cruts; Sandrine Radawiec; Franck Sturtz; E 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 69 KB 👁 2 views

Mutations in the presenilin-1 (PS1) gene account for the majority of familial early-onset Alzheimer's disease (EOAD) cases. We screened the coding part of the PS1 gene for the presence of mutations in a French family with EOAD, using single strand conformation polymorphism (SSCP) analysis. Patients

Sequence variants of the axin gene in br

Sequence variants of the axin gene in breast, colon, and other cancers: An analysis of mutations that interfere with GSK3 binding

✍ Marie-Therese Webster; Magdalena Rozycka; Elizabeth Sara; Elaine Davis; Matthew 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 164 KB 👁 1 views

Axin is a recently discovered component of a multiprotein complex containing APC, ␤-catenin, GSK3, and PP2A, which functions in the degradation of the ␤-catenin protein. As part of WNT signal transduction, the function of the Axin complex is inhibited, leading to the accumulation of ␤-catenin. The i

Allelic loss of the BRCA1 and BRCA2 gene

Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan (area of low incidence but early onset)

✍ Yen-Li Lo; Jyh-Cherng Yu; Chiun-Sheng Huang; Su-Ling Tseng; Tzu-Ming Chang; King 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 French ⚖ 456 KB 👁 1 views

We have examined the role of the breast cancer susceptibility genes BRCA1 and BRCA2 and other loci in the vicinity of these 2 genes on the long arms of chromosomes 17 and 13 (17q and 13q) for the presence of genomic deletions in breast cancer among Taiwanese women. Breast cancer in Taiwan is particu