Premium
Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability
Author(s) -
Herfarth Klaus K.F.,
Ogunbiyi Olagunju A.,
Moley Jeffrey F.,
Kodner Ira J.,
Wells Samuel A.,
Goodfellow Paul J.
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)12:1<73::aid-humu20>3.0.co;2-f
Subject(s) - mlh1 , biology , microsatellite instability , dna mismatch repair , genetics , point mutation , germline mutation , mutation , stop codon , gene , exon , dna repair , microbiology and biotechnology , cancer research , microsatellite , allele
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. Hum Mutat 12:73, 1998. © 1998 Wiley‐Liss, Inc.