PMID- 10521294
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 5
DP  - 1999 Nov
TI  - Association of hereditary nonpolyposis colorectal cancer-related tumors
      displaying low microsatellite instability with MSH6 germline mutations.
PG  - 1291-8
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) (Amsterdam criteria) is often
      caused by mutations in mismatch repair (MMR) genes, and tumors of patients with
      HNPCC show microsatellite instability (MSI-high phenotype). Germline mutations of
      MMR genes have rarely been found in families that have HNPCC or suspected HNPCC
      and that do not show microsatellite instability (MSI-low phenotype). Therefore,
      an MSI-high phenotype is often used as an inclusion criterion for mutation
      testing of MMR genes. Correction of base-base mismatches is the major function of
      MSH6. Since mismatches present with an MSI-low phenotype, we assumed that the
      phenotype in patients with HNPCC-related tumors might be associated with MSH6
      germline mutations. We divided 36 patients with suspected HNPCC into an MSI-low
      group (n=18) and an MSI-high group (n=18), on the basis of the results of MSI
      testing. Additionally, three unrelated patients from Amsterdam families with
      MSI-low tumors were investigated. All patients were screened for MSH2, MLH1, and 
      MSH6 mutations. Four presumably causative MSH6 mutations were detected in the
      patients (22%) who had suspected HNPCC and MSI-low tumors. Furthermore, we
      detected one frameshift mutation in one of the three patients with HNPCC and
      MSI-low tumors. In the MSI-high group, one MSH6 missense mutation was found, but 
      the same patient also had an MLH1 mutation, which may explain the MSI-high
      phenotype. These results suggest that MSH6 may be involved in a substantial
      proportion of patients with HNPCC or suspected HNPCC and MSI-low tumors. Our data
      emphasize that an MSI-low phenotype cannot be considered an exclusion criterion
      for mutation testing of MMR genes in general.
FAU - Wu, Y
AU  - Wu Y
AD  - Departments of Medical Genetics, University of Groningen, Groningen, The
      Netherlands.
FAU - Berends, M J
AU  - Berends MJ
FAU - Mensink, R G
AU  - Mensink RG
FAU - Kempinga, C
AU  - Kempinga C
FAU - Sijmons, R H
AU  - Sijmons RH
FAU - van Der Zee, A G
AU  - van Der Zee AG
FAU - Hollema, H
AU  - Hollema H
FAU - Kleibeuker, J H
AU  - Kleibeuker JH
FAU - Buys, C H
AU  - Buys CH
FAU - Hofstra, R M
AU  - Hofstra RM
LA  - eng
SI  - GENBANK/U73732
SI  - GENBANK/U73733
SI  - GENBANK/U73734
SI  - GENBANK/U73735
SI  - GENBANK/U73736
SI  - GENBANK/U73737
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (G-T mismatch-binding protein)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Base Pair Mismatch
MH  - Carrier Proteins
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics
MH  - DNA Mutational Analysis
MH  - DNA Repair
MH  - DNA-Binding Proteins/*genetics
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Exons
MH  - Female
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats/*genetics
MH  - Molecular Sequence Data
MH  - MutL Protein Homolog 1
MH  - MutS Homolog 2 Protein
MH  - Neoplasm Proteins
MH  - Nuclear Proteins
MH  - Pedigree
MH  - Proto-Oncogene Proteins/genetics
PMC - PMC1288281
EDAT- 1999/10/16 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/10/16 09:00
PHST- 1999/10/16 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/10/16 09:00 [entrez]
AID - S0002-9297(07)62135-1 [pii]
AID - 10.1086/302612 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Nov;65(5):1291-8. doi: 10.1086/302612.