PMID- 10480359
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 105
IP  - 1-2
DP  - 1999 Jul-Aug
TI  - Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes
      in 75 French kindreds with nonpolyposis colorectal cancer.
PG  - 79-85
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a syndrome characterized by 
      familial predisposition to colorectal carcinoma and extracolonic cancers of the
      gastrointestinal, urological, and female reproductive tracts. This dominant
      disorder is caused by germline defects in one of at least five DNA mismatch
      repair (MMR) genes: hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 (GTBP). Germline
      mutations of hMSH2 and hMLH1 are also frequently identified in families not
      fulfilling all the Amsterdam criteria, thereby demonstrating that the involvement
      of these genes is not confined to typical HNPCC. To evaluate the respective
      involvement of the various MMR genes in typical and incomplete HNPCC syndromes,
      we have performed an analysis of the hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes 
      in a large series of French kindreds (n=75) with colorectal tumors and/or
      aggregation of extracolonic cancers belonging to the HNPCC spectrum. Mutational
      analysis has been performed in all families, without preselection for the tumor
      phenotype. We have detected 26 pathogenic germline mutations of the hMLH1 and
      hMSH2 genes and several novel variants of the hPMS1, hPMS2, and hMSH6 genes. Our 
      data confirm that, regardless of the type of families and the tumor phenotype,
      hPMS1, hPMS2, and hMSH6 germline mutations are rare in familial aggregation of
      colorectal cancers. Furthermore, they suggest that the presence of multiple
      primary malignancies in a single individual and the observation of extracolonic
      tumors in relatives of a colorectal cancer patient should be included among the
      guidelines for referring patients for genetic testing.
FAU - Wang, Q
AU  - Wang Q
AD  - Departement d'Oncologie Fondamentale et Appliquee, INSERM Unite 453, Centre Leon 
      Berard, Lyon, France.
FAU - Lasset, C
AU  - Lasset C
FAU - Desseigne, F
AU  - Desseigne F
FAU - Saurin, J C
AU  - Saurin JC
FAU - Maugard, C
AU  - Maugard C
FAU - Navarro, C
AU  - Navarro C
FAU - Ruano, E
AU  - Ruano E
FAU - Descos, L
AU  - Descos L
FAU - Trillet-Lenoir, V
AU  - Trillet-Lenoir V
FAU - Bosset, J F
AU  - Bosset JF
FAU - Puisieux, A
AU  - Puisieux A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
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 (Nucleic Acid Heteroduplexes)
RN  - 0 (PMS1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.- (PMS2 protein, human)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (Mismatch Repair Endonuclease PMS2)
RN  - EC 3.6.1.3 (MutL Protein Homolog 1)
RN  - EC 3.6.1.3 (MutL Proteins)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - *Adenosine Triphosphatases
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Carrier Proteins
MH  - Colonic Neoplasms/genetics
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics
MH  - *DNA Repair Enzymes
MH  - DNA-Binding Proteins/genetics
MH  - France
MH  - Gene Deletion
MH  - Genetic Testing
MH  - *Germ-Line Mutation
MH  - Humans
MH  - Middle Aged
MH  - Mismatch Repair Endonuclease PMS2
MH  - MutL Protein Homolog 1
MH  - MutL Proteins
MH  - MutS Homolog 2 Protein
MH  - Neoplasm Proteins/*genetics
MH  - Nuclear Proteins
MH  - Nucleic Acid Heteroduplexes
MH  - Point Mutation
MH  - Prevalence
MH  - Proto-Oncogene Proteins/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/genetics
MH  - Urologic Neoplasms/genetics
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.1007/s004399900064 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Jul-Aug;105(1-2):79-85. doi: 10.1007/s004399900064.