Background: Precision oncology is advancing, increasing the demand for comprehensive, non-invasive genomic profiling tools. Liquid biopsy using circulating tumor DNA (ctDNA) enables real-time molecular profiling, treatment monitoring, and early detection of resistance variants. We developed the PAN100 panel (Dxome), a hybridization capture panel targeting 101 genes, as a pan-cancer genotyping assay to detect clinically actionable variants across various cancer types. This study presents the first comprehensive validation of the PAN100 panel including both analytical and clinical performance across eight cancer types using reference materials and matched tissue samples. Methods: For analytical validation, we assessed accuracy, limit of detection (LoD), and precision using Seraseq ctDNA v2 Reference Materials (SeraCare, Milford, MA, USA). Clinical validation was performed using plasma samples from 27 patients with eight types of cancer and 17 matched tumor samples. Positive percent agreement (PPA) between ctDNA and tissue next-generation sequencing (NGS) results was assessed using TruSight Oncology 500 and TruSight Tumor 170 assays. The limit of blank (LoB) was evaluated in 34 healthy individuals. Results: The PAN100 panel demonstrated high precision and linearity (LoD, 0.3%; 95.0% confidence interval, 0.29–0.35) variant allele frequency. The PPA between ctDNA and tissue NGS was 73.1% for single-nucleotide variants, 80.0% for insertions/deletions, and 74.2% overall. The LoB was 0.00001%. Conclusions The PAN100 panel is a robust tool for detecting clinically significant variants with high concordance with tissue NGS. Its sensitivity for low-frequency variants enables real-time treatment adaptation, supporting precision oncology. Its comprehensive design is particularly valuable for challenging diagnoses and clonal evolution monitoring.

Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Background: MUTYH-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of MUTYH-associated polyposis in East Asian and Korean populations, for which limited data were previously available. Methods: We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All MUTYH variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen. Results: The global carrier frequency of MUTYH-associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (nonFinnish) incidence of 1 in 11,520. Conclusions This was the first study to investigate the frequency of carriers of MUTYH-associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of MUTYH-associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.

Objectives: Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owingto the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2.Its Delta and Omicron variants are more transmissible and pathogenic than other variants.Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. Methods: The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared usingepidemiological data collected at the time of diagnosis. Results: The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. Conclusion Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load.