PMID- 10598809
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 105
IP  - 5
DP  - 1999 Nov
TI  - Missense mutations in hMLH1 associated with colorectal cancer.
PG  - 437-41
AB  - One of the most prevalent hereditary syndromes associated with colorectal cancer 
      is hereditary nonpolyposis colorectal cancer (HNPCC). The inherited gene defects 
      in HNPCC have been shown to reside in DNA mismatch repair genes, mostly hMSH2 or 
      hMLH1. Most HNPCC patients are heterozygous with regard to the relevant mismatch 
      repair gene; they have one normal and one mutated allele, and mismatch repair in 
      normal somatic cells is functional. Cancer predisposition in HNPCC is believed to
      be associated with the loss of the wild-type allele in somatic cells, resulting
      in defective DNA mismatch repair. This gives rise to DNA microsatellite
      instability (MSI), an increased somatic mutation rate, and eventually, to the
      accumulation of mutations in genes involved in colorectal carcinogenesis. In
      support of this theory, colorectal tumors in HNPCC patients and in mice deficient
      for hMSH2 or hMLH1 show MSI. Here, we describe two missense mutations in hMLH1
      exon 16 associated with colorectal cancer. Interestingly, the tumors do not show 
      MSI. This raises some potentially important issues. First, even
      microsatellite-negative colorectal tumors can be associated with germline
      mutations and these will be missed if an MSI test is used to select patients for 
      mutation screening. Second, the lack of MSI in these cases suggests that the
      mechanism involved in carcinogenesis could be different from that generally
      hypothesized.
FAU - Liu, T
AU  - Liu T
AD  - Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Tannergard, P
AU  - Tannergard P
FAU - Hackman, P
AU  - Hackman P
FAU - Rubio, C
AU  - Rubio C
FAU - Kressner, U
AU  - Kressner U
FAU - Lindmark, G
AU  - Lindmark G
FAU - Hellgren, D
AU  - Hellgren D
FAU - Lambert, B
AU  - Lambert B
FAU - Lindblom, A
AU  - Lindblom 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 Primers)
RN  - 0 (MLH1 protein, human)
RN  - 0 (Mlh1 protein, mouse)
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  - Animals
MH  - Base Pair Mismatch/genetics
MH  - Base Sequence
MH  - Carrier Proteins
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics
MH  - DNA Primers/genetics
MH  - DNA Repair/genetics
MH  - Exons
MH  - Female
MH  - Germ-Line Mutation
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Male
MH  - Mice
MH  - Microsatellite Repeats
MH  - MutL Protein Homolog 1
MH  - *Mutation, Missense
MH  - Neoplasm Proteins/*genetics
MH  - Nuclear Proteins
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1007/s004390051127 [doi]
PST - ppublish
SO  - Hum Genet. 1999 Nov;105(5):437-41. doi: 10.1007/s004390051127.