Article citationsMore>>
Murtaza, M., Dawson, S.J., Tsui, D.W., Gale, D., Forshew, T., Piskorz, A.M., Parkinson, C., Chin, S.F., Kingsbury, Z., Wong, A.S., Marass, F., Humphray, S., Hadfield, J., Bentley, D., Chin, T.M., Brenton, J.D., Caldas, C. and Rosenfeld, N. (2013) Non-Invasive Analysis of Acquired Resistance to Cancer Therapy by Sequencing of Plasma DNA. Nature, 497, 108-112.
https://doi.org/10.1038/nature12065
has been cited by the following article:
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TITLE:
Detection of the PIK3CA Mutation in Circulating Tumor DNA as a Possible Predictive Indicator for Poor Prognosis of Early-Stage Breast Cancer
AUTHORS:
Ayaka Sato, Masahiko Tanabe, Yumi Tsuboi, Masako Ikemura, Keiichiro Tada, Yasuyuki Seto, Yoshinori Murakami
KEYWORDS:
Early-Stage Breast Cancer, PIK3CA, Circulating Tumor DNA, Plasma, Droplet Digital PCR
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.1,
January
26,
2018
ABSTRACT: Objectives: Circulating tumor DNA (ctDNA) is shown to provide the real-time genomic information of metastatic breast cancer. This
study elucidates the clinico-pathological significance of ctDNA in early-stage breast
cancer using the PIK3CA mutation as an indicator. Materials and Methods: Twenty-seven primary breast cancers without metastasis were surgically resected and pathologically diagnosed at the University of Tokyo Hospital, Japan. Genomic
DNA of primary tumor was extracted from formalin-fixed and paraffin-embedded
specimens. ctDNA was extracted from fresh-frozen plasma from patients. The PIK3CA mutations at E542K, E545K and H1047R were
examined by Sanger sequencing or droplet digital PCR in 27 tumors and
pre- and post-surgery plasma. Results: The PIK3CA mutations were detected in
13 (48%) of 27 primary tumors. These mutations did not significantly correlate
with specific clinico-pathological characteristics of tumors. When ctDNA was
examined, 4 (33%) of 12 cases carrying the mutated PIK3CA showed the
identical mutation in pre-surgery plasma and 2 (50%) of them showed the identical
mutations in post-surgery plasma. Interestingly, in these 2 cases in
pathological stages IIIA and IA, fractional abundance of the mutated PIK3CA alleles to the total alleles in pre-surgery ctDNA was around 1% or more
and was higher than that of the other two cases without PIK3CA mutations in
post-surgery ctDNA. Conclusions: The PIK3CA mutation in ctDNA is detectable even
in a subset of early-stage breast cancer. Furthermore, fractional abundance of
the mutated PIK3CA in pre-surgery ctDNA could provide a possible predictive
indicator for tumor burden and for choosing the appropriate adjuvant treatment
of breast cancer.
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