PMID- 11309271
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 8
DP  - 2001 Apr 15
TI  - A mutator phenotype in cancer.
PG  - 3230-9
AB  - We have proposed that an early step in tumor progression is the expression of a 
      mutator phenotype resulting from mutations in genes that normally function in the 
      maintenance of genetic stability. There is new and strong experimental evidence 
      that supports the concept of a mutator phenotype in cancer. As technologies for 
      chromosomal visualization and DNA advance, there are increasing data that human 
      cancer cells contain large numbers of mutations. First, I will review the concept 
      of a mutator phenotype. Second, I will present the recent evidence that 
      individual cancer cells contain thousands of mutations. Third, I will explore 
      potential target genes that are required for maintenance of genetic stability in 
      normal cells and ask if they are mutated in cancer cells. Fourth, I will address 
      the timing of a mutator phenotype; is it an early event during tumor progression? 
      Do tumors already contain cells that harbor mutations rendering them resistant to 
      most chemotherapeutic agents? Lastly, I will speculate on the theoretical and 
      practical implication of a mutator phenotype in cancer and consider the 
      possibility of cancer prevention by delay, i.e., a reduction in mutation rates 
      early during carcinogenesis might slow the progression of tumors.
FAU - Loeb, L A
AU  - Loeb LA
AD  - Departments of Pathology and Biochemistry, The Joseph Gottstein Memorial Cancer 
      Research Laboratory, University of Washington, Seattle, WA 98195-7705, USA. 
      laloeb@u.washington.edu
LA  - eng
GR  - CA74184/CA/NCI NIH HHS/United States
GR  - CA80993/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mutation/*physiology
MH  - Neoplasms/*genetics
MH  - Phenotype
RF  - 101
EDAT- 2001/04/20 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/04/20 10:00
PHST- 2001/04/20 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/20 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Apr 15;61(8):3230-9.