PB2197 NEXT-GENERATION SEQUENCING IN CLINICAL PRACTICE: MOLECULAR EVENTS AND COURSE OF MYELOPROLIFERATIVE NEOPLASMS

e20506 Background: Differentiation of multiple primary lung cancer (MPLC) from intrapulmonary metastasis (IPM) is critical to determine clinical stage. Although clinicopathological features could provide certain evidences, it’s still challenging to identify the tumor malignancy accurately. In General, standard histopathologic approach is adequate in most cases, but has notable limitations in the recognition of IPMs. Herein, we propose an integrated molecular algorithm to facilitate MPLCs and IPMs diagnosis in the clinical practice. Methods: 40 Chinese patients with lung adenocarcinomas were enrolled in the study, 84 tumor samples were collected for next-generation sequencing. Somatic alterations with variant allele fraction (VAF) ≥1% were taken into account for molecular algorithm. A genomic database of 2,471 Chinese lung adenocarcinomas (LUAD) was used to calculate odds of coincidental occurrence, prevalence of individual mutation prevalence. Tumor relatedness diagnosed by histopathologic assessment was contrasted with comparative genomic profiling by subsequent NGS. Moreover, the performance of molecular algorithm prediction was evaluated as well. Results: Firstly, we compared the performance of comprehensive next-generation sequencing (NGS) with standard histopathologic approaches for distinguishing NSCLC subtypes in clinical practice. The genomic profiling was described as following: EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Further analysis showed that TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (22.9% vs 51.0%, P<0.05). TP53 alterations occurred less frequently in MPLCs compared to large Chinese cohort (P<0.05). The classifications based on the three different methodologies mentioned above were compared. Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%), particularly in the prediction of MPLC. Retrospective review highlighted several histologic challenges, including morphologic progression in some IPMs. For the five undetermined cases, two showed differences in architectural patterns, and remained cases have nodules presented as adenocarcinoma in situ, or minimally invasive adenocarcinoma. Of 28 MPLC cases defined by NGS, 25 cases had unique somatic mutations per pair Based on calculation from the prevalence of EGFR L858R mutation (27%) in large Chinese cohort, the odds of coincidental occurrence of the mutation in two unrelated tumors was 7.3%. Taking together, EGFR alterations occurred more frequently in MPLCs compared to IPMs (77.1% vs 50.0%, P<0.05). Molecular algorithm prediction was concordant with NGS in 21 cases (52.5%). Conclusions: Our results support broad panel NGS to assist differential diagnosis to assist approach in clinical practice. It is necessary to conduct large clinical study to establish comprehensive algorithm models to assist diagnosis and predict clinical outcome.

Download Full-text

The genetic analysis of Chinese patients with clonal cytopenias using targeted next-generation sequencing

Molecular Cytogenetics ◽

10.1186/s13039-021-00572-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Lijuan Zhang ◽

YuYe Shi ◽

Yue Chen ◽

Shandong Tao ◽

Wenting Shi ◽

...

Keyword(s):

Next Generation Sequencing ◽

Myelodysplastic Syndromes ◽

Rna Splicing ◽

Myeloproliferative Neoplasms ◽

Chinese Patients ◽

Newly Diagnosed ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Significant Difference ◽

Generation Sequencing

Abstract Background Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. Methods Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. Results Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. Conclusion NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice.

Download Full-text

Integrating a Next Generation Sequencing Panel into Clinical Practice in Ovarian Cancer

Yonsei Medical Journal ◽

10.3349/ymj.2019.60.10.914 ◽

2019 ◽

Vol 60 (10) ◽

pp. 914 ◽

Cited By ~ 1

Author(s):

Yong Jae Lee ◽

Dachan Kim ◽

Hyun-Soo Kim ◽

Kiyong Na ◽

Jung-Yun Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Practice ◽

Next Generation Sequencing ◽

Next Generation ◽

Generation Sequencing

Download Full-text

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

10.21203/rs.3.rs-483741/v1 ◽

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.

Download Full-text