The feasibility of circulating tumor DNA analysis as a marker of recurrence in triple-negative breast cancer （トリプルネガティブ乳癌における，血中循環腫瘍DNAの遺伝子解析と再発マーカ―としての可能性に関する検討）
著者
岡崎, 智
(Okazaki, Satoshi)
上位タイトル
Oncology letters
Vol.21,
No.5
(2021.
5)
,p.420-
識別番号
ISSN
1792-1074
DOI
10.3892/ol.2021.12681
その他
PMID:33841581
博士論文情報
学位授与番号
10107A556
学位授与年月日
2021-03-25
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Triple-negative breast cancer (TNBC) has a poorer prognosis than other breast cancer subtypes; therefore, identifying markers of early recurrence is important. The present study aimed to establish a liquid biopsy protocol for droplet digital PCR-based detection of frequently mutated genes in patients with TNBC. Tumor DNA from 36 patients with TNBC who relapsed within 2 years after surgical resection was retrospectively analyzed. Somatic mutational profiles were evaluated using targeted sequencing to identify frequently mutated genes and genes associated with molecularly targeted therapies. The association between genetic alterations and associated protein phosphorylation was investigated using immunohistochemical analysis. Recurrent hot spot mutations in the plasma were monitored over time. Mutation-specific probes were used to successfully detect mutations in the blood samples of patients who were positive for PIK3CA H1047R and AKT1 E17K mutations. Somatic mutations in AKT1 (14.9%) and PIK3CA (25.5%) were frequently identified in the data. Robust phosphorylation of AKT and S6RP was more common in tumors with PIK3CA H1047R and AKT1 E17K mutational background than in tumors with wild-type PIK3CA and AKT1. In conclusion, the present study evaluated a high-sensitivity detection system for frequently mutated genes that was also applicable for cell-free DNA. The PI3K/AKT pathway was revealed to be activated in patients harboring PIK3CA H1047R and AKT1 E17K mutations; therefore, the PI3K/AKT pathway may be a promising candidate for targeted therapy in these patients.
