PMID- 10573010
OWN - NLM
STAT- MEDLINE
DCOM- 20000120
LR  - 20161124
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 7
DP  - 1999 Oct-Nov
TI  - Assessment of pathogenicity criteria for constitutional missense mutations of the
      hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2.
PG  - 778-82
AB  - To determine the role played by MLH1 and MSH2 missense variants in cancer
      susceptibility, we have investigated the following genetic and biological
      characteristics associated with six MLH1 and four MSH2 missense changes
      identified in Italian hereditary nonpolyposis colorectal cancer (HNPCC) families:
      co-segregation with disease phenotype and/or bonafide pathogenetic mutations;
      presence of the variant in healthy control subjects; evolutionary conservation of
      the involved aminoacid and type of aminoacid change; and presence/absence of
      microsatellite instability (MSI) in tumour DNA. Overall, nine variants did not
      fulfil > or = 2 pathogenicity criteria. MSI was investigated in tumour samples
      from carriers of nine different missense mutations. Only 3/9 variants were
      associated with MSI in tumour DNA. In addition, four variants were not present in
      affected pedigree members, and five variants were observed in the control
      population. Based upon these results, we conclude that most MLH1 and MSH2
      missense changes are unlikely to act as major causative factors in colorectal
      cancer susceptibility and development.
FAU - Genuardi, M
AU  - Genuardi M
AD  - Institute of Medical Genetics, A Gemelli School of Medicine, Universita Cattolica
      del Sacro Cuore, Rome , Italy. mgenuardi@rm.unicatt.it
FAU - Carrara, S
AU  - Carrara S
FAU - Anti, M
AU  - Anti M
FAU - Ponz de Leon, M
AU  - Ponz de Leon M
FAU - Viel, A
AU  - Viel A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
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  - Adolescent
MH  - Adult
MH  - Carrier Proteins
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics
MH  - DNA, Neoplasm/analysis
MH  - *DNA-Binding Proteins
MH  - Genetic Predisposition to Disease/*genetics
MH  - Humans
MH  - Microsatellite Repeats/genetics
MH  - MutL Protein Homolog 1
MH  - MutS Homolog 2 Protein
MH  - *Mutation, Missense
MH  - Neoplasm Proteins/*genetics
MH  - Nuclear Proteins
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200363 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Oct-Nov;7(7):778-82. doi: 10.1038/sj.ejhg.5200363.