Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases
Abstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to AL...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Thoracic Cancer |
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| Online Access: | https://doi.org/10.1111/1759-7714.14936 |
| _version_ | 1797788563738198016 |
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| author | Liang Shi Lili Guo Hong Tao Qiyi Meng Li Tong Junfang Tang Kun Li Shucai Zhang Zhe Liu |
| author_facet | Liang Shi Lili Guo Hong Tao Qiyi Meng Li Tong Junfang Tang Kun Li Shucai Zhang Zhe Liu |
| author_sort | Liang Shi |
| collection | DOAJ |
| description | Abstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes. |
| first_indexed | 2024-03-13T01:38:20Z |
| format | Article |
| id | doaj.art-f368edc694b446b98237211faf71f7ac |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-03-13T01:38:20Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-f368edc694b446b98237211faf71f7ac2023-07-04T00:04:28ZengWileyThoracic Cancer1759-77061759-77142023-07-0114191883189310.1111/1759-7714.14936Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastasesLiang Shi0Lili Guo1Hong Tao2Qiyi Meng3Li Tong4Junfang Tang5Kun Li6Shucai Zhang7Zhe Liu8Department of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Pathology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaDepartment of Medical Oncology, Beijing Chest Hospital Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing ChinaAbstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes.https://doi.org/10.1111/1759-7714.14936ALKbrain metastasescerebrospinal fluidlung adenocarcinomanext‐generation sequencing |
| spellingShingle | Liang Shi Lili Guo Hong Tao Qiyi Meng Li Tong Junfang Tang Kun Li Shucai Zhang Zhe Liu Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases Thoracic Cancer ALK brain metastases cerebrospinal fluid lung adenocarcinoma next‐generation sequencing |
| title | Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases |
| title_full | Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases |
| title_fullStr | Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases |
| title_full_unstemmed | Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases |
| title_short | Genetic profiling of circulating cell‐free DNA from cerebrospinal fluid and paired plasma in ALK‐positive lung cancer with brain metastases |
| title_sort | genetic profiling of circulating cell free dna from cerebrospinal fluid and paired plasma in alk positive lung cancer with brain metastases |
| topic | ALK brain metastases cerebrospinal fluid lung adenocarcinoma next‐generation sequencing |
| url | https://doi.org/10.1111/1759-7714.14936 |
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