PMID- 9192806
OWN - NLM
STAT- MEDLINE
DCOM- 19970715
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 12
DP  - 1997 Jun 15
TI  - Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal 
      tumors.
PG  - 2350-3
AB  - The E2F group of transcription factors transactivates genes that promote 
      progression through the G1-S transition of the cell cycle. Members of the 
      retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function. 
      E2F-4, one example of the E2F group, functions as an oncogene when transfected 
      into nontransformed cells in vitro. On the other hand, mice that are homozygously 
      lacking a normal E2F-1 gene develop cancers, consistent with a tumor-suppressive 
      role for this gene. The exact function of E2Fs has thus been unclear; moreover, 
      direct involvement of this gene in primary human tumorigenesis has not been 
      shown. We, therefore, investigated mutation within the E2F-4 coding region in 16 
      primary gastric adenocarcinomas, 12 ulcerative colitis-associated neoplasms, 46 
      sporadic colorectal carcinomas, 9 endometrial cancers, and 3 prostatic 
      carcinomas. We limited our investigation to the serine repeat within E2F-4, 
      reasoning that this tract might be altered in genetically unstable tumors 
      (replication error-positive, or RER+). All tumors were RER+, with the exception 
      of a control group of 15 RER- sporadic colorectal carcinomas. PCR with 
      incorporation of [32P]dCTP was performed using primers flanking the serine 
      trinucleotide (AGC) repeat. Twenty-two of 59 gastrointestinal tumors (37%) 
      contained E2F-4 mutations; these comprised 5 of 16 gastric tumors (31%), 4 of 12 
      ulcerative colitis-associated neoplasms (33%, including 1 dysplastic lesion), and 
      13 of 31 sporadic colorectal cancers (42%). No mutation was present in any of the 
      endometrial, prostate, or RER- colorectal tumors. Of note, homozygous mutations 
      occurred in three cases, and two of seven informative patients showed loss of one 
      E2F-4 allele in their tumors. Furthermore, the RER+ sporadic colorectal tumors 
      were evaluated at trinucleotide repeats within the genes for N-cadherin and 
      B-catenin; no tumors demonstrated mutation of these genes. These data suggest 
      that E2F-4 is a target of defective DNA repair in these tumors.
FAU - Souza, R F
AU  - Souza RF
AD  - Department of Medicine, University of Maryland School of Medicine and Baltimore 
      Veterans Affairs Medical Center, 21201-1595, USA.
FAU - Yin, J
AU  - Yin J
FAU - Smolinski, K N
AU  - Smolinski KN
FAU - Zou, T T
AU  - Zou TT
FAU - Wang, S
AU  - Wang S
FAU - Shi, Y Q
AU  - Shi YQ
FAU - Rhyu, M G
AU  - Rhyu MG
FAU - Cottrell, J
AU  - Cottrell J
FAU - Abraham, J M
AU  - Abraham JM
FAU - Biden, K
AU  - Biden K
FAU - Simms, L
AU  - Simms L
FAU - Leggett, B
AU  - Leggett B
FAU - Bova, G S
AU  - Bova GS
FAU - Frank, T
AU  - Frank T
FAU - Powell, S M
AU  - Powell SM
FAU - Sugimura, H
AU  - Sugimura H
FAU - Young, J
AU  - Young J
FAU - Harpaz, N
AU  - Harpaz N
FAU - Shimizu, K
AU  - Shimizu K
FAU - Matsubara, N
AU  - Matsubara N
FAU - Meltzer, S J
AU  - Meltzer SJ
LA  - eng
GR  - CA67497/CA/NCI NIH HHS/United States
GR  - DK47717/DK/NIDDK NIH HHS/United States
GR  - ES07120/ES/NIEHS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F4 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Alleles
MH  - Cadherins/genetics
MH  - Chromosome Deletion
MH  - Cytoskeletal Proteins/genetics
MH  - DNA, Neoplasm/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - E2F4 Transcription Factor
MH  - Endometrial Neoplasms/genetics
MH  - Female
MH  - Gastrointestinal Neoplasms/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Prostatic Neoplasms/genetics
MH  - *Trans-Activators
MH  - Transcription Factors/*genetics
MH  - beta Catenin
EDAT- 1997/06/15 00:00
MHDA- 1997/06/15 00:01
CRDT- 1997/06/15 00:00
PHST- 1997/06/15 00:00 [pubmed]
PHST- 1997/06/15 00:01 [medline]
PHST- 1997/06/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Jun 15;57(12):2350-3.