Classification of somatic variants in solid tumors detected by next-generation sequencing (NGS) and the need for clinical guidelines.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1555-1555
Author(s):  
Antonios Papanicolau-Sengos ◽  
Edward Hart ◽  
Wei Shen ◽  
Kenneth F. Grossmann ◽  
Cecily Vaughn ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Clinical Guidelines ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Next-Generation Sequencing Mutational Landscape and Clinical Features of Chinese Adults with Myeloproliferative Neoplasms

2021 ◽  
Author(s):  
Shuna Luo ◽  
Zanzan Wang ◽  
Xiaofei Xu ◽  
Lan Zhang ◽  
Shengjie Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Comprehensive Evaluation ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Next Generation ◽  
Chinese Adults ◽  
Leukocyte Counts ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: Myeloproliferative neoplasms (MPNs) include three classical subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN, it has been a subject of debate among experts due to its indefinite diagnosis. However, pre-PMF usually has a distinct outcome compared with either ET or overt PMF. In this study, we examined the clinical, haematologic, genetic, and prognostic differences among pre-PMF, ET, and overt PMF.Methods: We retrospectively reviewed the clinical parameters, haematologic information, and genetic mutations of patients who were diagnosed with pre-PMF, ET, and overt PMF according to the WHO 2016 criteria using next-generation sequencing (NGS).Results: Pre-PMF patients exhibited higher leukocyte counts, higher LDH values, a higher frequency of splenomegaly, and a higher incidence of hypertension than ET patients. On the other hand, pre-PMF patients had higher platelet counts and haemoglobin levels than overt PMF patients. Molecular analysis revealed that the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients. In terms of outcome, male sex, along with symptoms including MPN-10, anaemia, thrombocytopenia, and KMT2A and CUX1 mutations, indicated a poor prognosis for PMF patients.Conclusion: The results of this study indicated that comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.

Mutational landscape of AKT1/2/3 in Chinese patients with solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15566-e15566
Author(s):  
Hui Kong ◽  
Weijia Fang ◽  
Haibo Mou ◽  
Feng Xiao Chen ◽  
Lingxiang Liu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Chinese Patients ◽  
Great Promise ◽  
Central Component ◽  
Next Generation ◽  
Gene Panel Testing ◽  
Different Types ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

e15566 Background: As a central component of PI3K/AKT pathway, AKT serves as an attractive target of anti-cancer strategy with various AKT inhibitors, which show great promise in phase I/II clinical trials. This study aimed to investigate AKT1/2/3 status in different types of cancers by using next generation sequencing (NGS). Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 10,010 Chinese patients with solid tumors and subjected to next-generation sequencing (NGS)-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB) values, and microsatellite instability (MSI) status were assessed with a mean coverage of 1000X, including single base substitutions, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements. Genomic data and immune checkpoint inhibitors (ICIs) treatment outcome of a cohort of 1610 patients with solid tumors were derived from cBioPortal (MSKCC, Nat Genet. 2019). Results: AKT1/2/3 were found to be mutually exclusive with each other and accounted for 3.4% in this cohort. The frequencies of AKT1/2/3 variations were 1.1%, 1.6%, and 0.8%, respectively. The most common co-altered genes associated with AKT1/2/3 variations were TP53 (69.4%), PIK3CA (19.3%), KRAS (19%), CCNE1 (18.4%), CDKN2A (16.6%), and 11q13 (6.5%). AKT1/2/3 variations were significantly associated with higher TMB, and independent of MSI status. Outcome data from the MSKCC cohort showed that patients with AKT1/2/3 variations had a remarkable clinical benefit to ICIs treatment compared to patients with wild-type AKT1/2/3 in overall survival (OS) (NA vs 18 months, p = 0.009). Furthermore, AKT1/2/3 variations were independent risk factors of OS (HR: 0.55, 95%CI: 0.34-0.87, p = 0.012). Conclusions: The prevalence of AKT1/2/3 somatic alterations across different types of solid tumors in China was 3.4%. AKT1/2/3 variations were associated with an increased TMB and favorable response to ICIs, suggesting that A KT1/2/3 variations may be biomarkers for guiding anti-AKT agents and ICI treatment.

ERBB2 mutation profiling with next-generation sequencing (NGS) in solid tumors.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24264-e24264
Author(s):  
Fei Ma ◽  
Min Zhang ◽  
Quchang Ouyang ◽  
Jun Zhao ◽  
Xiaorong Dong ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumors ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing ◽  
Mutation Profiling

scholarly journals Real-world Concordance in Microsatellite Instability Status Between PCR-based Testing and Next-Generation Sequencing Assay for Solid Tumors

2021 ◽  
Author(s):  
Keitaro Shimozaki ◽  
Hideyuki Hayashi ◽  
Sara Horie ◽  
Akihiko Chida ◽  
Kai Tsugaru ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Solid Tumors ◽  
Real World ◽  
Next Generation ◽  
Predictive Values ◽  
Primary Endpoints ◽  
Repair Deficiency ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Background: Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, which can detect MSI status using a polymerase chain reaction (PCR)-based method, was approved as the first tumor-agnostic companion diagnostic for pembrolizumab in patients with MSI-H solid tumors in Japan. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available. However, the real-world concordance in MSI-H/dMMR between the PCR-based testing and NGS is yet to be thoroughly investigated.Methods: A retrospective study was conducted to evaluate the utility of MSI testing using PCR-based testing and NGS assay in patients eligible for both MSI testing and any NGS platform. Co-primary endpoints included positive and negative predictive values of MSI-H/dMMR.Results: Between December 2018 and June 2020, 40 patients underwent both PCR-based MSI testing and NGS assay for MSI. Two patients with gastric neuroendocrine carcinoma and ovarian cancer were confirmed to have MSI-H/dMMR in both examinations. Among the 38 patients diagnosed as microsatellite stable by PCR-based testing, 2 (5.2%) with pancreatic cancer were diagnosed as MSI-H after NGS analyses. NGS had positive and negative predictive values of 100% (2/2) and 94.7% (36/38), respectively, for MSI-H, while the concordance between NGS and PCR-based testing was 94.9% (38/40).Conclusion: Similar to PCR-based MSI testing, NGS can be useful for evaluating MSI/MMR status in clinical practice and could be an important alternative method for detecting MSI-H/dMMR in the future.

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