MYC amplification and TERT expression in breast tumor progression.
The complex roles of genomic instability, MYC oncogene amplification, activation of telomerase, and p53 function still remain to be fully described in breast tumors. MYC stimulates the telomerase catalytic subunit, TERT, which interacts with p53. Oncogene MYC amplification analysis was performed on 27 paraffin-embedded breast tumor samples by fluorescence in situ hybridization, selected on the basis of chromosomal instability. TERT immunostaining was performed on a larger group of breast tumor sections. All tumor samples were analyzed for TP53 mutation, genomic index, S-phase fraction, and pathological stages. Amplification of MYC was detected in 16 of 27 tumors (59%) and found to be associated with TNM stages I and II (P = 0.018), genomic index > 1.5 (P = 0.033), and S-phase fraction > 5% (P = 0.020). No association was found between MYC amplification and TERT immunostaining or TP53 mutations. Analysis of TERT in 103 primary breast tumors showed > 50% nuclei immunostaining in 58% of cases. High TERT immunostaining associated with genomic index > 1.5 (P = 0.017), high S-phase fraction (P = 0.056), and TP53 mutations (P = 0.030). No association was found between TERT staining and TNM stages. This study supports early involvement of MYC amplification in breast tumor progression. Both MYC amplification and TERT expression appear to be associated with high genomic instability and proliferation. TERT association with TP53 mutations indicates that TERT activity is downregulated by functional p53 protein in breast tumors.
Bodvarsdóttir
Sigríthur K
SK
Department of Medicine, University of Iceland, Vatnsmýrarvegi 16, 101 Reykjavik, Iceland.
Steinarsdóttir
Margrét
M
Hilmarsdóttir
Hólmfríthur
H
Jónasson
Jón G
JG
Eyfjörd
Jorunn E
JE
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005784:Gene Amplification / Q000502:physiology*; D016259:Genes, myc; D016158:Genes, p53; D042822:Genomic Instability; D006801:Humans; D007621:Karyotyping; D009154:Mutation / Q000502:physiology; D016196:S Phase; D019098:Telomerase / Q000235:genetics*; D014407:Tumor Cells, Cultured
C509186:TERT protein, human; D019098:Telomerase