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Measurable residual disease (MRD) in acute myeloid leukemia (AML) refers to the quantity of residual leukemic cells in a patient after treatment.According to the latest agreements, MRD in AML offering essential prognostic insights. However, there is ongoing debate regarding MRD-based monitoring and treatment strategies. There are multiple platforms for detecting MRD, each varying in sensitivity and suitability for different patients. MRD not only predicts treatment outcomes but also serves as an indicator of treatment effectiveness and a prognostic biomarker. In AML, most retrospective studies indicate that patients who are MRD-positive or show increasing MRD levels at specific time points during remission have significantly higher risks of relapse and mortality compared to MRD-negative patients. Although achieving MRD-negative status can improve patient prognosis, the possibility of relapse remains. Despite the correlation between MRD and clinical outcomes, MRD assessment methods are not yet standardized, leading to discrepancies in results across different techniques. To provide reliable MRD results, it is essential to optimize and standardize MRD detection methods. Methods for assessing MRD include multiparameter flow cytometry (MFC) and molecular assays, chosen based on disease characteristics. This review focuses on currently available MRD detection methods and discusses how the prognostic value of MRD test results informs personalized treatment strategies for AML patients. [ABSTRACT FROM AUTHOR]

Purpose Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer. Materials and Methods We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500. Results The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation. Conclusion NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies. [ABSTRACT FROM AUTHOR]

Background: The anaplastic lymphoma kinase (ALK) mutation, also known as the diamond mutation in non-small-cell lung cancer (NSCLC), has been treated with tremendous success since it was first reported in 2007. Alectinib, a second generation ALK-Tyrosine kinase inhibitor (TKI), has been reported to have significantly longer progression-free survival (PFS) than first generation ALK inhibitors in untreated ALK positive NSCLC. However, the clinical efficacy of ALK-TKIs on rare ALK fusions remains unclear. In recent years, with the popularity of next-generation sequencing (NGS) technology, an increasing number of novel ALK fusion partners have been reported, but the responses are heterogeneous among different ALK fusions. Considering the inconsistent reactions, the clinical efficacy of ALK-TKIs in rare ALK gene fusions remains to be evaluated in more cases. Methods: To seek for individualized therapy, the tumor tissues acquired during biopsy were sent for genomic testing by NGS based on a 139-gene panel and a 425-gene panel in a centralized clinical testing center (GENESEEQ Technology Inc, Nanjing, China). See Supplementary Material for more details about the methods for DNA-based NGS, RNA-based NGS. Results: We present two cases of patients with lung adenocarcinoma harboring two novel Intergenic Region (IGR)-ALK rearrangements detected by DNA sequencing, which had limited clinical response to ALK-TKIs but showed sensitivity to chemotherapy combined with bevacizumab therapy in patient 2, with a PFS of over 1 year up till the last follow-up assessment. Conclusions: In summary, our cases emphasize the need for comprehensive molecular analysis of different ALK fusion partners at the DNA level to formulate accurate treatment strategies and provide a certain therapeutic reference for these two types of novel IGR-ALK fusions. [ABSTRACT FROM AUTHOR]

Abstract Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.

Objective To evaluate the capability of metagenomic next-generation sequencing （mNGS）in the pathogen diagnosis of periprosthetic joint infection（PJI）in order to provide clinical experience of choosing diagnostic methods. Methods From Jan 2017 to Dec 2019，patients with borderline symptoms were involved in this study.Intraoperative synovial fluid and periprosthetic tissues were both collected for microbial culture and mNGS.The pathogens were identified by symptoms, therapy and positive results. Results According to the criteria of Musculoskeletal Infection Society（MSIS）13 patients were diagnosed as PJI.The positive rate of mNGS was 84.62%, which was higher than that of culture method （76.92%). aphylococcus aureus, Enterococcus faecium, Candida albicans and Mycoplasma hominis were the main detected pathogens of PJI.The detection time of mNGS was 48 h, which was significantly shorter than culture method（14 d） . Conclusion With higher speed of detection in PJI, mNGS can provide vital etiological evidence for early accurate diagnosis of PJI.mNGS is an effectivecomplementtomicrobialculturemethod，especiallyinculture-negative PJI. [ABSTRACT FROM AUTHOR]

Background: Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods: Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results: Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions: RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal. [ABSTRACT FROM AUTHOR]

BRAF and NRAS genetic analyses are time-consuming and can delay treatment choices in patients with metastatic melanomas presenting with acute deterioration. We compared the rapid, real-time, fully automated molecular diagnosis platform Idylla™ with next-generation sequencing (NGS) and immunohistochemistry for detection of BRAF and NRAS mutations in 36 patients with metastatic melanomas. The Idylla™ NRAS-BRAF-EGFRS492R mutation assay (110 min per sample) detected BRAF and NRAS mutations in 15 and 17 samples, respectively. One NRAS mutation was different between NGS and Idylla™ (NRASG13C vs. NRASG12A/D). Four samples were BRAF and NRAS wild-type. The global concordance between NGS and Idylla™ assays was 97.2% (35/36 cases). Immunohistochemistry was positive only in 9/9 BRAFV600E- and 6/6 NRASQ61R-mutated samples with VE1 and SP174 antibodies, respectively. The Idylla™ platform is a valuable rapid molecular diagnosis tool to reduce the delay in BRAF and NRAS analyses-related treatment choices for patients with metastatic melanoma presenting with acute deterioration.

• Norovirus and rotavirus alone are responsible for ^30% of all cases of diarrhea worldwide. • Despite global improvement in hygienic measurements and vaccine development, enteric viruses still pose a considerable burden. • NGS is a reliable and effective surveillance-method for enteric diseases providing important information in a timely manner. • Further development of NGS with a reduction in the costs is the most useful tool in the ongoing monitoring of norovirus and rotavirus diseases. • Surveillance of enterovirus morbidity and mortality is far from over with the development of effective vaccines. Enteric viruses, particularly rotaviruses and noroviruses, are leading causes of gastroenteritis worldwide. Human rotaviruses are ubiquitous and globally almost every child has been infected by 3–5 years of age. Noroviruses affect people of all ages and is the leading cause of foodborne outbreaks. Rota- and noroviruses account for ˜40% and ˜17% of diarrhea-associated hospitalizations, and ˜200,000 deaths annually respectively, with most deaths occurring in developing countries. Two rotavirus vaccines have currently been implemented in ˜95 countries and several norovirus vaccine candidates are currently in development and/or clinical testing. Surveillance of enteric viruses is an important part of outbreak investigations as well as pre- and post-vaccine impact studies but is even in developed countries often limited to investigation of sporadic cases or comprehensive outbreaks. Conventional methods for enteric virus detection and subtyping relies on standard RT-PCR methods, supplemented with Sanger-sequencing. However, for viruses with even moderate mutationrates, PCR-based-typing of only limited parts of the virus genome is challenging and requires regular update of primers. Full-genomecharacterization technologies based on sequence independent methods based on next generation sequencing (NGS), have demonstrated great potential for enteric virus detection and/or typing in both clinical and environmental samples. However, cost-benefits must balance for such methods to be widely accepted for public health purposes. In Europe as also globally, routine use of NGS-methods for surveillance of enteric viruses is currently limited to few national public health laboratories. What important lessons can be learned from these and what is the future of NGS-based surveillance? [ABSTRACT FROM AUTHOR]

Background: Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. Results: SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genomewide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. Conclusions: This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of undetermined significance (MGUS) is defined as a clinically silent, symptom-free state that does not meet the diagnostic criteria of multiple myeloma (MM), Waldenstrom macroglobulinemia, AL-amyloidosis or any other malignant lymphoproliferative disease. Long-term follow-up has demonstrated that this may be a pre-cancerous state with transformation into a malignant monoclonal gammopathy in approximately 1% of cases annually. Probably all cases of MM arise as a transformation of MGUS. In this overview, the author attempts to answer the key question, namely whether it is currently possible in some way to prevent the transformation of MGUS into MM or to at least to slow this down. The answer in MGUS patients is currently unequivocally NO. In view of the significantly higher risk of transformation in patients with asymptomatic multiple myeloma than in patients with MGUS, further analysis by the CMG will focus on this group of patients with the goal of selecting the group at highest risk and to subject this group to early and if possible nontoxictreatment. [ABSTRACT FROM AUTHOR]