PMID- 10627141
OWN - NLM
STAT- MEDLINE
DCOM- 20000105
LR  - 20161124
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 12
IP  - 1
DP  - 1998
TI  - Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers
      with microsatellite instability. Mutations in brief no. 157. Online.
PG  - 73
AB  - 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 a 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 ammino 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 MLHI mutations identified appear to be causally
      associated with the RER phenotype.
FAU - Klaus, K
AU  - Klaus K
AD  - Department of Surgery, Washington University School of Medicine, St. Louis,
      Missouri, USA.
FAU - Herfarth, F
AU  - Herfarth F
FAU - Ogunbiyi, O A
AU  - Ogunbiyi OA
FAU - Moley, J F
AU  - Moley JF
FAU - Kodner, I J
AU  - Kodner IJ
FAU - Wells, S A Jr
AU  - Wells SA Jr
FAU - Goodfellow, P J
AU  - Goodfellow PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Base Pair Mismatch/*genetics
MH  - Carrier Proteins
MH  - Colorectal Neoplasms/*genetics
MH  - DNA Repair/*genetics
MH  - Humans
MH  - MutL Protein Homolog 1
MH  - Mutation/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Nuclear Proteins
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - Trinucleotide Repeat Expansion/*genetics
EDAT- 2000/01/08 09:00
MHDA- 2000/06/22 10:00
CRDT- 2000/01/08 09:00
PHST- 2000/01/08 09:00 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 2000/01/08 09:00 [entrez]
AID - 10.1002/(SICI)1098-1004(1998)12:1<73::AID-HUMU20>3.0.CO;2-F [pii]
AID - 10.1002/(SICI)1098-1004(1998)12:1<73::AID-HUMU20>3.0.CO;2-F [doi]
PST - ppublish
SO  - Hum Mutat. 1998;12(1):73. doi:
      10.1002/(SICI)1098-1004(1998)12:1<73::AID-HUMU20>3.0.CO;2-F.