Detection of TP53/PIK3CA Mutations in Cell-Free Plasma DNA From Metastatic Breast Cancer Patients Using Next Generation Sequencing.
Circulating tumor DNA (ctDNA) within a liquid biopsy is a promising marker for genotyping metastatic tumors.



We performed next generation whole exon sequencing of TP53 and PIK3CA genes, which are the 2 most common genetic alterations in breast cancer, in plasma DNA (pDNA) of 17 metastatic breast cancer (MBC) patients and in tumor DNA (tDNA) from their primary tumors.



We identified 11 mutations (6 in TP53 and 5 in PIK3CA) in tDNA from 8 patients (47%) and 13 mutations (6 in TP53 and 7 in PIK3CA) in pDNA from 7 patients (41%). Six mutations in pDNA were also identified in tDNA but seven were not. Six MBC patients with TP53 and/or PIK3CA mutations in pDNA had a significantly worse survival rate (P < .05) after recurrence than that of the other 8 MBC patients without these mutations. Carcinoembryonic antigen and cancer antigen 15-3 levels did not correlate with prognosis (P = .675 and P = .877, respectively).



These results suggest that mutations in ctDNA can be detected with next generation sequencing in MBC patients and could be a more useful prognostic factor for survival after recurrence than conventional tumor markers.
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Chiaki
C
Nakauchi
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: kagaran@onsurg.med.osaka-u.ac.jp.
Naofumi
N
Kagara
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Kenzo
K
Shimazu
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Atsushi
A
Shimomura
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Yasuto
Y
Naoi
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Masafumi
M
Shimoda
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Seung Jin
SJ
Kim
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Shinzaburo
S
Noguchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D017422:Sequence Analysis, DNA / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
Acquired mutation; Circulating tumor DNA; Liquid biopsy; Next generation sequencer; Prognostic biomarker