PMID- 15010897
OWN - NLM
STAT- MEDLINE
DCOM- 20041129
LR  - 20061115
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 11
IP  - 4
DP  - 2004 Apr
TI  - Apoptotic and growth regulatory genes as mutational targets in mismatch repair 
      deficient endometrioid adenocarcinomas of young patients.
PG  - 931-7
AB  - Among multiple genetic pathways involved in endometrial cancer (EC), the mutator 
      pathway is characterized by defective mismatch repair (MMR) causing 
      microsatellite instability (MSI+). Inactivation of MMR genes allows elevation of 
      mutation rates in key target genes involved in important cellular pathways, 
      providing a selective growth advantage. Our aim was to investigate apoptotic and 
      growth regulatory target genes in young endometrioid adenocarcinoma patients and 
      their association with stepwise neoplastic progression through distinct stages of 
      hyperplasia and cancer. Screening of 184 ECs revealed 38 microsatellite high 
      (MSI-H), 10 microsatellite low (MSI-L) and 136 microsatellite stable (MSS) 
      tumors. We observed somatic frameshift mutations in the coding region repeats of 
      the target genes in 12/38 MSI-H tumors (T) and in 3/8 of available associated 
      hyperplasias (HY). Mutations were detected in FAS (T=1, HY=1), BAX (T=6, HY=1), 
      CASP5 (T=2) and IGFIIR (T=3, HY=1) genes. None of the MSI-L or MSS tumors showed 
      alterations in these coding repeats. Increased mutation frequency in apoptotic 
      and growth regulatory genes demonstrated a significant relationship with 
      advancing tumor grade (p=0.02) by Fisher's exact test. Furthermore, a significant 
      trend was found by Bartholomew's test (P<0.05) for the apoptotic pathway and 
      close to significant (p approximately 0.06) for the overall mutation status for 
      both pathways combined. Our results suggest that genes implicated in apoptosis 
      may serve as targets in the progression of MSI+ EC in young patients.
FAU - Vassileva, Vessela
AU  - Vassileva V
AD  - Samuel Lunenfeld Research Institute, Toronto, Canada.
FAU - Millar, Anna
AU  - Millar A
FAU - Briollais, Laurent
AU  - Briollais L
FAU - Chapman, William
AU  - Chapman W
FAU - Bapat, Bharati
AU  - Bapat B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Receptors, Growth Factor)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/genetics/pathology
MH  - Adult
MH  - Apoptosis/*genetics
MH  - DNA Mutational Analysis
MH  - DNA Repair/genetics
MH  - Endometrial Neoplasms/*diagnosis/genetics/pathology
MH  - Female
MH  - Gene Targeting
MH  - Humans
MH  - Microsatellite Repeats/genetics
MH  - Middle Aged
MH  - *Mutation
MH  - Receptors, Growth Factor/*genetics
EDAT- 2004/03/11 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/03/11 05:00
PHST- 2004/03/11 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/03/11 05:00 [entrez]
PST - ppublish
SO  - Oncol Rep. 2004 Apr;11(4):931-7.