Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumininduced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumin-inhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

Purpose: Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles. Materials and Methods: We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas. Results: The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus. Conclusion The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

Purpose: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay. Materials and Methods: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. Results: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. Conclusion The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.