Dataset Information

Molecular characterization of MET fusions from a large real-world Chinese population: A multicenter study.

ABSTRACT:

Purpose

MET is a notable driver gene in the diversity of aberrations with clinical relevance, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two, MET fusions are severely under-reported, leaving a series of unanswered questions. In this study, we addressed this gap by characterizing MET fusions in a large, real-world Chinese cancer population.

Methods

We retrospectively included patients with solid tumors who had DNA-based genome profiles acquired through targeted sequencing from August 2015 to May 2021. MET fusion-positive (MET+) patients were subsequently selected for clinical and molecular characterization.

Results

We screened 79,803 patients across 27 tumor types and detected 155 putative MET fusions from 122 patients, resulting in an overall prevalence of 0.15%. Lung cancer comprised the majority of MET+ patients (92, 75.4%). Prevalence was markedly higher in liver cancer, biliary tract cancer, and renal cancer (range 0.52%-0.60%). It was lower in ovarian cancer (0.06%). A substantial proportion (48/58, 82.8%) of unique partners were reported for the first time. High heterogeneity was observed for partners, with ST7, HLA-DRB1, and KIF5B as the three most common partners. Mutational landscape analysis of lung adenocarcinoma (n = 32) revealed a high prevalence of TP53 in MET+ alterations, EGFR L858R, EGFR L861Q, and MET amplification.

Conclusion

To our knowledge, this is currently the largest study in characterizing MET fusions. Our findings warrant that further clinical validation and mechanistic study may translate into therapeutic avenues for MET+ cancer patients.

SUBMITTER: Xia H

PROVIDER: S-EPMC10358190 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Molecular characterization of MET fusions from a large real-world Chinese population: A multicenter study.

Xia Hui H Zhang Junhua J Chen Tong T Wang Mingzhao M Chen Dongna D Si Tongguo T Liu Yutao Y

Cancer medicine 20230616 13

<h4>Purpose</h4>MET is a notable driver gene in the diversity of aberrations with clinical relevance, including exon 14 skipping, copy number gain, point mutations, and gene fusions. Compared with the former two, MET fusions are severely under-reported, leaving a series of unanswered questions. In this study, we addressed this gap by characterizing MET fusions in a large, real-world Chinese cancer population.<h4>Methods</h4>We retrospectively included patients with solid tumors who had DNA-based ...[more]

PMID: 37326363

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Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) patients refractory to rituximab-based immunochemotherapy have a dismal prognosis. However, the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries. To validate the definition and outcomes of refractory DLBCL in China, we conducted a multicenter, retrospective cohort study.MethodsThe REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL (REAL-TREND) study was performed using real-world data from 8 centers in China. DLBCL patients with curative intent were included in the REAL-TREND dataset. Overall survival (OS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Due to heterogeneity in response rates among different centers, the response rates of refractory patients were pooled using random-effect models. Multivariate survival analysis was performed using the Cox regression model.ResultsA total of 2778 DLBCL patients diagnosed between January, 2010 and December, 2015 were enrolled to this study. After validating previous definitions, the SCHOLAR-1 study was most suitable to define refractory DLBCL. The estimated 5-year cumulative incidence of refractory patients was 20% (95% confidence Interval [CI] = 18%-22%). After the determination of refractory disease, overall response rate and complete remission rate were 30% (95% CI = 22%-38%) and 9% (95% CI = 4%-15%), respectively. Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months (95% CI = 5.5-7.1 months) and 2-year OS rate of 16% (95% CI = 12%-20%). International prognostic index score 4-5 (hazard ratio [HR] = 2.22; 95% CI = 1.47-3.35), central nervous system relapse (HR = 1.43; 95% CI = 1.04-1.97), and best response status (HR = 2.68; 95% CI = 1.42-5.03 for partial remission. HR = 5.97, 95% CI = 3.21-11.11 for stable disease/progressive disease) were independent unfavorable prognostic factors.ConclusionsThis is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL. The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival, thus is appropriate to select refractory DLBCL. Due to poor clinical outcomes in the rituximab era, patients with refractory DLBCL may be potential candidates for novel treatment modalities.

Dataset Information

Molecular characterization of MET fusions from a large real-world Chinese population: A multicenter study.

Purpose

Methods

Results

Conclusion

Publications

Molecular characterization of MET fusions from a large real-world Chinese population: A multicenter study.

Similar Datasets

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