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番号	年度	題名	雑誌	リンクを見る
12	2023	Practical Utility of Liquid Biopsy for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer Abstract Traditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples fr\|om patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid®100-HRR panel. Plasma samples fr\|om a total of 87 patients were included in this study. Somatic mutations fr\|om cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes fr\|om their cfDNA. Archival tissue samples fr\|om 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations. Practical Utility of Liquid Biopsy for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer リンクを見る	Cancers	リンクを見る
11	2023	Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA Abstact Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cfDNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy. Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA リンクを見る	Cancer Research and Treatment	リンクを見る
10	2023	Marked Response to Larotrectinib in Pelvic Spindle Cell Sarcoma With Concurrent TPM3-NTRK1 Fusion and CDK4/MDM2 Amplification: A Case Report Background Primary pelvic sarcoma is rare and often involves adjacent organs including rectum and urinary bladder because of the anatomic constraints of the pelvis.1 This may impede the attempts to achieve wide excision with tumor-free margins. Here, we reported that perioperative targeted therapy against tyrosine receptor kinase is a promising therapeutic approach to significantly improve surgical outcomes in huge pelvic spindle cell sarcoma with neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Marked Response to Larotrectinib in Pelvic Spindle Cell Sarcoma With Concurrent TPM3-NTRK1 Fusion and CDK4/MDM2 Amplification: A Case Report リンクを見る	JCO Precision Oncology	リンクを見る
9	2022	Differentially hypomethylated cell‑free DNA and coronary collateral circulation Background: The factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronarycollateral circulation (CCC). Result: In this case–control study, clinical and angiographic data were obtained fr\|om 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted fr\|om the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions fr\|om which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Differentially hypomethylated cell‑free DNA and coronary collateral circulation リンクを見る	Clinical Epigenetics	リンクを見る
8	2022	Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment BackgroundCirculating tumour DNA (ctDNA) has been spotlighted as an attractive biomarker because of its easy accessibility and real-time representation of tumour genetic profile. However, the clinical utility of longitudinal ctDNA monitoring has not been clearly defined.MethodsSerial blood samples were obtained fr\|om metastatic colorectal cancer patients undergoing first-line chemotherapy. ctDNA was sequenced using a targeted next-generation sequencing platform which included 106 genes. Changes in ctDNA profile and treatment outcome were comprehensively analysed.ResultsA total of 272 samples fr\|om 62 patients were analysed. In all, 90.3% of patients had detectable ctDNA mutation before treatment. ctDNA clearance after chemotherapy was associated with longer progression-free survival which was independent of radiological response (adjusted hazard ratio 0.22, 95% confidence interval 0.10–0.46). Longitudinal monitoring was able to detect ctDNA progression which preceded radiological progressive disease (PD) in 58.1% (median 3.3 months). Diverse resistant mutations (34.9%) and gene amplification (7.0%) at the time of PD were discovered. For 16.3% of the PD patients, the newly identified mutations could be potential candidates of targeted therapy or clinical trial.ConclusionctDNA profile provided a more accurate landscape of tumour and dynamic changes compared to radiological evaluation. Longitudinal ctDNA monitoring may improve personalised treatment decision-making. Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment リンクを見る	British Journal of Cancer	リンクを見る