𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability

✍ Scribed by Klaus K.-F. Herfarth; Olagunju A. Ogunbiyi; Jeffrey F. Moley; Ira J. Kodner; Samuel A. Wells Jr.; Paul J. Goodfellow

Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
35 KB
Volume
12
Category
Article
ISSN
1059-7794

No coin nor oath required. For personal study only.

✦ Synopsis

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with inherited mutation in one of four DNA mismatch repair genes. Somatic mutations in the same genes are also found in a subset of sporadic colorectal cancers. A defect in DNA mismatch repair results in an RER (replication error) tumor phenotype. We screened 110 archival and 11 prospectively acquired colorectal cancers for the RER phenotype. A total of 22 cancers were RER-positive. RER-positive tumors were investigated for mutations in the DNA mismatch repair gene MLH1 using single-strand-conformation-polymorphism (SSCP) analysis. We identified four previously undescribed mutations in four different samples. Three mutations were exonic: a point mutation at codon 69 (AGG -> AAG [arg -> lys]); a single base pair deletion at codon 42/43 (GCAAAATCC -> GCAAATCC) leading to a new stop codon downstream; and a point mutation at codon 757 (TAA ->TAT [termination -> tyr] which extend the MLH1 peptide by 36 amino acids. The fourth mutation was a 1 base pair insertion six base pairs 5' to the start of exon 14 (tttgtttt -> tttggtttt). The mutations were not seen in the patients' constitutional DNA. The somatic MLH1 mutations identified appear to be causally associated with the RER phenotype.

πŸ“œ SIMILAR VOLUMES

Microsatellite instability as a predicto
Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer
✍ Tao Liu; Siobhan Wahlberg; Eva Burek; Per Lindblom; Carlos Rubio; Annika Lindblo πŸ“‚ Article πŸ“… 2000 πŸ› John Wiley and Sons 🌐 English βš– 122 KB πŸ‘ 1 views

Germline alterations in human DNA mismatch repair genes are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Mutation analysis of the genes reveals carriers with a high risk of colorectal cancer, who will benefit from surveillance. We wanted to find the best predictive parameter of

Mutations in MLH1 are more frequent than
Mutations in MLH1 are more frequent than in MSH2 in sporadic colorectal cancers with microsatellite instability
✍ Klaus K.-F. Herfarth; Ira J. Kodner; Alison J. Whelan; Jennifer L. Ivanovich; Jo πŸ“‚ Article πŸ“… 1997 πŸ› John Wiley and Sons 🌐 English βš– 158 KB πŸ‘ 2 views

The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. Microsatellite instab

Mean age of tumor onset in hereditary no
Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes
✍ Valeria Pensotti; Paolo Radice; Silvano Presciuttini; Daniele Calistri; Isabella πŸ“‚ Article πŸ“… 1997 πŸ› John Wiley and Sons 🌐 English βš– 105 KB πŸ‘ 2 views

Fourteen Italian families affected with hereditary nonpolyposis colorectal cancer (HNPCC) were screened for germline mutations at three DNA mismatch repair (MMR) genes, MSH2, MLH1, and GTBP, by using a combination of different methods that included an in vitro synthesized protein assay, single-stran

Mutation sharing, predominant involvemen
Mutation sharing, predominant involvement of the MLH1 gene and description of four novel mutations in hereditary nonpolyposis colorectal cancer
✍ Mari Holmberg; Paula Kristo; Robert B. Chadwicks; Jukka-Pekka Mecklin; Heikki JΓ€ πŸ“‚ Article πŸ“… 1998 πŸ› John Wiley and Sons 🌐 English βš– 37 KB πŸ‘ 2 views

Worldwide, the DNA mismatch repair genes MSH2 and MLH1 account for a major share and almost equal proportions of hereditary nonpolyposis colorectal cancer (HNPCC). Furthermore, the predisposing mutation usually varies from kindred to kindred. In this study, we screened 29 verified or putative HNPCC

Hypermethylation of the Myf-3 gene in co
Hypermethylation of the Myf-3 gene in colorectal cancers: Associations with pathological features and with microsatellite instability
✍ Beverley Shannon; Peter Kay; Anthony House; Barry Iacopetta πŸ“‚ Article πŸ“… 1999 πŸ› John Wiley and Sons 🌐 French βš– 70 KB πŸ‘ 1 views

Myf-3 is the human homologue of the murine Myo-D1 gene involved in muscle-cell differentiation. Using Southern blot analysis, we examined methylation of Myf-3 in histologically normal colonic mucosae, adenomas and carcinomas from a large series of patients with primary colorectal cancer. Hypermethyl