Germline truncating mutations in both MSH2 and BRCA2 in a single kindred
| Autor: | D Du Sart, J Deschênes, Isabelle Thiffault, N Hamel, David E. Goldgar, E. MacNamara, Victoria Marcus, Shannon Cowie, Wendy S. Meschino, William D. Foulkes, D. Farber, Fabrice Odefrey, Steven A. Narod, Tuya Pal, George Chong, T Graham, A K Watters, Susan McVety |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Cancer Research DNA Complementary DNA Repair Genetic Linkage DNA Mutational Analysis Genes BRCA2 Molecular Sequence Data colorectal cancer Breast Neoplasms Biology Polymerase Chain Reaction Neoplasms Multiple Primary Exon Germline mutation breast cancer Proto-Oncogene Proteins medicine Humans astrocytoma neoplasms multiple primary cancers Germ-Line Mutation Aged Genetics Base Sequence Breakpoint Microsatellite instability Proteins Genetics and Genomics Middle Aged medicine.disease BRCA2 Immunohistochemistry MSH2 Pedigree DNA-Binding Proteins MutS Homolog 2 Protein Oncology Mutation (genetic algorithm) Mutation testing Microsatellite microsatellite instability Female Colorectal Neoplasms |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone. |
| Databáze: | OpenAIRE |
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