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Mutational and Loss of Heterozygosity Analysis of the p53 and PTENTumor Suppressor Genes in Breast Carcinoma

Mutational and Loss of Heterozygosity Analysis of the p53 and PTEN Tumor Suppressor Genes in Breast Carcinoma

이영호|박문일|김헌수|나선영|서광선|이생금
대한병리학회|2005.10|Journal of Pathology and Translational Medicine|제39권 제5호|pp. 313-319

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초록

Abstract

Background : Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas. Methods : Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN. Results : Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018). Conclusions : Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.

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