In:
Cancer Science, Wiley, Vol. 109, No. 8 ( 2018-08), p. 2558-2566
Abstract:
PIK 3 CA mutations are common activating mutations associated with breast cancer (occurring in 20–30% of all cases) and are potent predictive markers for responses to PI 3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method using a quenching probe ( QP ) system to identify PIK 3 CA mutations, using DNA from 309 breast cancer tissues. In a developmental cohort, we determined the optimal detection threshold of the QP system with human tumor DNA from 119 freshly frozen tumor samples. We found a 96% concordance rate with the QP system between DNA from 26 matching fresh‐frozen specimens and formalin‐fixed paraffin‐embedded ( FFPE ) specimens from the same patients, and known PIK 3 CA mutation status in the developmental cohort. In a validation cohort, we evaluated whether the threshold for judging mutations using the QP system with frozen specimen‐derived DNA was applicable with FFPE ‐derived DNA . In the validation cohort, 30 DNA samples from 190 FFPE ‐derived DNA samples with known PIK 3 CA mutation status were analyzed by direct sequencing ( DS ) and droplet digital PCR, in a blinded manner. The sensitivity and specificity of the droplet digital PCR results were 100% and 100% ( QP system), and 60% and 100% ( DS ), respectively. We also analyzed the relationship between clinical outcomes and the PIK 3 CA mutational status of 309 breast cancer samples, including the developmental cohort and validation cohort samples. Multivariate analysis suggested that PIK 3 CA mutations, especially H1047R, were prognostic factors of relapse‐free survival. Our novel detection system could be more useful than DS for detecting clinical PIK 3 CA mutations.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2018.109.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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