Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients

  • Authors:
    • Vessela Vassileva
    • Anna Millar
    • Laurent Briollais
    • William Chapman
    • Bharati Bapat
  • View Affiliations

  • Published online on: April 1, 2004     https://doi.org/10.3892/or.11.4.931
  • Pages: 931-937
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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≈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.

Related Articles

Journal Cover

April 2004
Volume 11 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Vassileva V, Millar A, Briollais L, Chapman W and Bapat B: Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients. Oncol Rep 11: 931-937, 2004
APA
Vassileva, V., Millar, A., Briollais, L., Chapman, W., & Bapat, B. (2004). Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients. Oncology Reports, 11, 931-937. https://doi.org/10.3892/or.11.4.931
MLA
Vassileva, V., Millar, A., Briollais, L., Chapman, W., Bapat, B."Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients". Oncology Reports 11.4 (2004): 931-937.
Chicago
Vassileva, V., Millar, A., Briollais, L., Chapman, W., Bapat, B."Apoptotic and growth regulatory genes as mutational targets in mismatch repair deficient endometrioid adenocarcinomas of young patients". Oncology Reports 11, no. 4 (2004): 931-937. https://doi.org/10.3892/or.11.4.931