ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

Wang, Zheng; Wu, Xiaonan; Han, Xiaohong; Cheng, Gang; Mu, Xinlin; Zhang, Yuhui; Cui, Di; Liu, Chang; Liu, Dongge; Shi, Yuankai

doi:10.21147/j.issn.1000-9604.2016.06.07

Cited by 7 publications

(5 citation statements)

References 35 publications

(28 reference statements)

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“…ALK stimulates hypoxia pathways via direct regulation of HIF1α and HIF2α expression, promoting angiogenesis, and subsequently increasing pleural membrane permeability (113). ALK + EML4 gene fusion has been reported in ~5% of patients with MPE using immunohistochemistry, fluorescence in situ hybridization or RT-PCR (114)(115)(116). The present study identified 6 patients (5.5%), one male and five females, with the ALK + EML4 gene fusion using NGS.…”

Section: Discussionmentioning

confidence: 75%

Multiplexed molecular profiling of lung cancer with malignant pleural effusion using next generation sequencing in Chinese patients

Ruan

Sun²,

Wang³

et al. 2020

Oncol Lett

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Lung cancer is the most common type of cancer and the leading cause of cancer-associated death worldwide. Malignant pleural effusion (MPE), which is observed in ~50% of advanced non-small cell lung cancer (NSCLC) cases, and most frequently in lung adenocarcinoma, is a common complication of stage III-IV NSCLC, and it can be used to predict a poor prognosis. In the present study, multiple oncogene mutations were detected, including 17 genes closely associated with initiation of advanced lung cancer, in 108 MPE samples using next generation sequencing (NGS). The NGS data of the present study had broader coverage, deeper sequencing depth and higher capture efficiency compared with NGS findings of previous studies on MPE. In the present study, using NGS, it was demonstrated that 93 patients (86%) harbored EGFR mutations and 62 patients possessed mutations in EGFR exons 18-21, which are targets of available treatment agents. EGFR L858R and exon 19 indel mutations were the most frequently observed alterations, with frequencies of 31 and 25%, respectively. In 1 patient, an EGFR amplification was identified and 6 patients possessed a T790M mutation. ALK + EML4 gene fusions were identified in 6 patients, a ROS1 + CD74 gene fusion was detected in 1 patient and 10 patients possessed a BIM (also known as BCL2L11) 2,903-bp intron deletion. In 4 patients, significant KRAS mutations (G12D, G12S, G13C and A146T) were observed, which are associated with resistance to afatinib, icotinib, erlotinib and gefitinib. There were 83 patients with ERBB2 mutations, but only two of these mutations were targets of available treatments. The results of the present study indicate that MPE is a reliable specimen for NGS based detection of somatic mutations.

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Section: Discussionmentioning

confidence: 75%

Multiplexed molecular profiling of lung cancer with malignant pleural effusion using next generation sequencing in Chinese patients

Ruan

Sun²,

Wang³

et al. 2020

Oncol Lett

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“…ese findings suggest low level of cf-RNA burden in sera. Previous studies have showed that MPE cell blocks can be used for ALK gene rearrangement detection [2,4]. Hence, in this study, we compared the mutation status in cf-RNA of sera and the supernatant to the mutation status in the cell blocks from the same patients.…”

Section: Discussionmentioning

confidence: 99%

“…Lung cancer is the leading cause of cancer death among both men and women, of which non-small-cell lung cancer (NSCLC) represents approximately 85% of the total cases diagnosed [1]. Driver gene abnormality tests are the premise of targeted therapy for advanced NSCLC, particularly in the adenocarcinoma subtype [2]. Among these, EGFR gene mutations and ALK gene rearrangement are widely recognized alterations that respond to target agents in NSCLC [3].…”

Section: Introductionmentioning

confidence: 99%

Detection of ALK Gene Rearrangement in Cell-free RNA from Lung Cancer Malignant Pleural Effusion

Chu

Zhu

et al. 2020

BioMed Research International

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The aim of this study was to evaluate the feasibility of measuring ALK gene rearrangement in cell-free RNA (cf-RNA) of the supernatant from malignant pleural effusion (MPE). Supernatant, cell blocks, and matched sera samples were collected. Cf-RNA was isolated from the supernatant and sera, and cellular RNA was isolated from cell blocks. The ALK gene rearrangement in the cf-RNA was tested by the real-time polymerase chain reaction. Results showed that the concentration of cf-RNA was higher in the supernatant than in matched sera. ALK status concordance rates were 100% between the supernatant and cell blocks, while they were 0% between sera and cell blocks in ALK gene rearrangement cases. This suggests that using cf-RNA in MPE supernatant, but not in sera, could offer a reliable and robust surrogate strategy for the detection of ALK gene rearrangement.

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“…RT‐PCR is a good candidate method for detecting EML4‐ALK in blocks of pleural effusion cells from lung cancer patients. Table summarizes the main studies on the detection of ALK translocations in MPE …”

Section: Implications Of New Therapies In Nsclcmentioning

confidence: 99%

“…Table 2 summarizes the main studies on the detection of ALK translocations in MPE. 31,[39][40][41][42][43]…”

Section: Eml4/alk Translocationsmentioning

confidence: 99%

Novel insights into the systemic treatment of lung cancer malignant pleural effusion

Tissot

Gay

Brun

et al. 2019

Clinical Respiratory J

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Lung cancer is the most common fatal malignancy worldwide. Approximately 75% of non‐small‐cell lung cancer (NSCLC) patients are diagnosed at an advanced or a metastatic stage. Since 2007, NSCLC patients with malignant pleural effusion (MPE) are staged as M1 disease. During the last decades, chemotherapeutic agents failed to offer a significant improvement of survival in patients with metastatic disease. The current review aims to summarize the actual situation of the recently developed therapies in patients with lung cancer and MPE.

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ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

Cited by 7 publications

References 35 publications

Multiplexed molecular profiling of lung cancer with malignant pleural effusion using next generation sequencing in Chinese patients

Multiplexed molecular profiling of lung cancer with malignant pleural effusion using next generation sequencing in Chinese patients

Detection of ALK Gene Rearrangement in Cell-free RNA from Lung Cancer Malignant Pleural Effusion

Novel insights into the systemic treatment of lung cancer malignant pleural effusion

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