PMID- 10537275
OWN - NLM
STAT- MEDLINE
DCOM- 19991110
LR  - 20161124
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 20
DP  - 1999 Oct 15
TI  - Germ-line msh6 mutations in colorectal cancer families.
PG  - 5068-74
AB  - Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to
      inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas
      germ-line mutations in other mismatch repair genes are rare. We examined the
      frequency of germ-line msh6 mutations in a population-based series of 140
      colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC
      cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases,
      germ-line msh6 mutations were found in 6 patients (7.1% of probands analyzed;
      median age at diagnosis, 61 years). These mutations included a splice site
      mutation, a frameshift mutation, two missense mutations that were demonstrated to
      be loss of function mutations, and two missense mutations for which functional
      studies were not possible. In contrast, germ-line msh6 mutations were not found
      in any of the 45 sporadic cases and the 4 HNPCC cases in the population-based
      series or in the second series of 58 clinic-based, primarily HNPCC families. Our 
      data suggest that germ-line msh6 mutations predispose individuals to primarily
      late-onset, familial colorectal carcinomas that do not fulfill classic criteria
      for HNPCC.
FAU - Kolodner, R D
AU  - Kolodner RD
AD  - Ludwig Institute for Cancer Research, Department of Medicine and Cancer Center,
      University of California San Diego Medical School, La Jolla 92093-0660, USA.
      rkolodner@ucsd.edu
FAU - Tytell, J D
AU  - Tytell JD
FAU - Schmeits, J L
AU  - Schmeits JL
FAU - Kane, M F
AU  - Kane MF
FAU - Gupta, R D
AU  - Gupta RD
FAU - Weger, J
AU  - Weger J
FAU - Wahlberg, S
AU  - Wahlberg S
FAU - Fox, E A
AU  - Fox EA
FAU - Peel, D
AU  - Peel D
FAU - Ziogas, A
AU  - Ziogas A
FAU - Garber, J E
AU  - Garber JE
FAU - Syngal, S
AU  - Syngal S
FAU - Anton-Culver, H
AU  - Anton-Culver H
FAU - Li, F P
AU  - Li FP
LA  - eng
GR  - CA67151/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (MLH1 protein, human)
RN  - 0 (MSH6 protein, S cerevisiae)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Aged
MH  - Carrier Proteins
MH  - Colorectal Neoplasms/*genetics
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/genetics
MH  - *DNA-Binding Proteins
MH  - Fungal Proteins/*genetics
MH  - *Germ-Line Mutation
MH  - Heterozygote
MH  - Humans
MH  - Middle Aged
MH  - MutL Protein Homolog 1
MH  - Neoplasm Proteins/genetics
MH  - Nuclear Proteins
MH  - *Saccharomyces cerevisiae Proteins
EDAT- 1999/10/28 00:00
MHDA- 1999/10/28 00:01
CRDT- 1999/10/28 00:00
PHST- 1999/10/28 00:00 [pubmed]
PHST- 1999/10/28 00:01 [medline]
PHST- 1999/10/28 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Oct 15;59(20):5068-74.