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  • Title: PIK3CA mutations mostly begin to develop in ductal carcinoma of the breast.
    Author: Li H, Zhu R, Wang L, Zhu T, Li Q, Chen Q, Wang H, Zhu H.
    Journal: Exp Mol Pathol; 2010 Feb; 88(1):150-5. PubMed ID: 19818761.
    Abstract:
    Somatic mutations of PIK3CA are found in 20% to 40% of invasive breast cancers. To investigate the frequency of PIK3CA mutations in the intraductal proliferative lesions of the breast, which are precursor lesions for invasive carcinoma, we analyzed 125 intraductal proliferative lesions and 108 invasive breast cancer tissues for PIK3CA mutations in this study. Target cells were precisely isolated using a laser capture microdissection (LCM) system. Genomic DNA was extracted with QIAmp DNA Micro Kit. PCR amplification was done for exons 9 and 20 of PIK3CA, where 90% of mutations clustered, and the products were directly sequenced. Forty-six missense mutations were identified in total, of which, 14 and 32 mutations clustered in exon 9 and exon 20, respectively. The most common mutations were E542K (6 cases) and E545K (8 cases) in exon 9, and H1047R (29 cases) in exon 20. A novel mutation, G3292T, was also found. Mutations were found less frequently in the ductal intraepithelial neoplasia 1B (DIN1B) and lower grade ductal proliferative lesions (3 of 68; 4.41%) than in ductal carcinoma in situ (14 of 57; 24.56%, P=0.001, Chi-square test) or invasive carcinoma (29 of 108; 26.85%, P=0.000, Chi-square test). However, there was no significant difference in the frequency of PIK3CA mutations between carcinoma in situ and invasive carcinoma (P=0.750, Chi-square test). PIK3CA mutations mostly began to develop at the stage from the DIN1B to the carcinoma in situ (DCIS), which is a late event of breast oncogenesis. PIK3CA-mutated tumors were more frequently found in ER-a positive, PR positive, and PTEN positive tumors (P=0.012, P=0.004 and P=0.004, respectively, Chi-square test). The frequency of PIK3CA gene mutation in ER+/PR+ (32/98, 32.65%) tumors was not significantly different from that in ER+/PR- (9/39, 23.08%), tested by the Chi-square test (P=0.269). There was no significant association between PIK3CA mutations and HER2 expression status (P=0.294, Chi-square test).
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