J Breast Cancer.  2007 Mar;10(1):68-76. 10.4048/jbc.2007.10.1.68.

Loss of Heterozygosity of Major Tumor Suppressor Genes in Invasive Ductal Carcinomas

• Byun WS
• Park CH
• Cho SJ
• Ahn HG
• Nam ES
• Cha HJ
• Kim KS

• KMID: 2175003
• DOI: http://doi.org/10.4048/jbc.2007.10.1.68

Abstract

PURPOSE: Breast cancer is one of the most frequent malignant tumors in Korea. The major tumor suppressor genes (TSGs) such as p16, Rb, E-cadherin and p53 may play important roles in cell cycle regulation, apoptosis and the regulation of the expression of other genes as well as tumor suppression. Microsatellite alteration such as loss of heterozygosity (LOH) have been reported to be a novel mechanism of carcinogenesis and a useful prognostic factor for many malignant tumors. Also, LOH is also known to be related with allelic loss of various TSGs. This study evaluated LOH of 4 TSGs in invasive ductal carcinomas (IDCs) and we correlated these results with the clinicopathological factors.
METHODS
LOH analysis was carried out using a polymerase chain reaction with 12 polymorphic microsatellite markers of 4 TSGs in 50 surgically resected tumors and their non-tumorous counterparts.
RESULTS
There was no detectable LOH in the normal tissue. LOH was detected in 86% of the 50 cases of IDCs. LOH was detected on all chromosomes and this showed a statistical difference between benign tumor and malignant tumor. LOH of p16, Rb, E-cadherin and p53 TSGs was detected in 36%, 26%, 54% and 60% of the tumors, respectively. LOH of the p16 and Rb genes was inversely correlated with tumor grade 1. The low rate of detecting LOH on the E-cadherin gene was noted in T1 tumor and stage I disease. LOH of the p53 gene correlated well with the tumor size and stage. The LOH-High results correlate well with the tumor size and stage and the LOH-High results are similar to those of the p53 gene LOH.
CONCLUSION
These results suggest that LOH of the 4 major TSGs may contribute to the development and invasion of IDCs. Also, the combined use of various LOH markers may help in deciding the prognosis of IDCs.

Keyword

Invasive ductal carcinoma; Tumor suppressor gene; LOH

MeSH Terms

Apoptosis
Breast Neoplasms
Cadherins
Carcinogenesis
Carcinoma, Ductal*
Cell Cycle
Genes, p53
Genes, Retinoblastoma
Genes, Tumor Suppressor*
Korea
Loss of Heterozygosity*
Microsatellite Repeats
Polymerase Chain Reaction
Prognosis
Cadherins

Figure

• 

  Fig 1 Representative LOH pattern on p16, Rb, E-cadherin and p53 gene in invasive ductal carcinoma. Each LOH detection was accomplished at the microsatellite markers (D9S104, D13S118, D16S419, TP53) of the each invasive ductal carcinoma. Each T lane shows near-entirely or considerable band loss. N=normal; T=tumor.

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