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PIK3CA Mutations in In situ and Invasive Breast Carcinomas

Cited 93 time in Web of Science Cited 96 time in Scopus
Authors
Miron, Alexander; Varadi, Maria; Carrasco, Daniel; Li, Hailun; Kim, Hee Jung; Cho, Eun Yoon; Kehoe, Sarah; Dillon, Deborah; Macconaill, Laura; Polyak, Kornelia; Gelman, Rebecca; Allred, D. Craig; Iglehart, J. Dirk; Lewis, Gretchen; Park, So Yeon; Luongo, Lauren
Issue Date
2010-07-15
Publisher
AMER ASSOC CANCER RESEARCH
Citation
CANCER RESEARCH; Vol.70 14; 5674-5678
Keywords
DCISPIK3CAtumor progressioninvasionbreast cancer
Abstract
The PIK3 signaling pathway has been identified as one of the most important and most frequently mutated pathways in breast cancer. Somatic mutations in the catalytic subunit of PIK3CA have been found in a significant fraction of breast carcinomas, and it has been proposed that mutant PIK3CA plays a role in tumor initiation. However, the majority of primary human tumors analyzed for genetic alterations in PIK3CA have been invasive breast carcinomas and the frequency of PIK3CA mutations in preinvasive lesions has not been explored. To investigate this, we sequenced exons 9 and 20 of PIK3CA in pure ductal carcinoma in situ ( DCIS), DCIS adjacent to invasive carcinoma, and invasive ductal breast carcinomas. In a subset of cases, both in situ and invasive areas were analyzed from the same tumor. We found that the frequency of PIK3CA mutations was essentially the same (similar to 30%) in all three histologic groups. In some cases, in situ and invasive areas of the same tumor were discordant for PIK3CA status, and in two cases in which multiple invasive and adjacent in situ areas within the same tumor were analyzed independently, we detected intratumor heterogeneity for PIK3CA mutations. Our results suggest that mutation of PIK3CA is an early event in breast cancer that is more likely to play a role in breast tumor initiation than in invasive progression, although a potential role for exon 9 mutations in the progression of a subset of DCIS cases cannot be excluded. Cancer Res; 70(14); 5674-8. (C)2010 AACR.
ISSN
0008-5472
Language
English
URI
https://hdl.handle.net/10371/76667
DOI
https://doi.org/10.1158/0008-5472.CAN-08-2660
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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