Mengxi Ge1, Qiong Zhan1, Zhenzhen Zhang2, Xiaoyu Ji1, Xinli Zhou1, Ruofan Huang3, Xiaohua Liang4. 1. Department of Oncology, Huashan Hospital Fudan University, Shanghai, China. 2. Singlera Genomics Inc., Shanghai, China. 3. Department of Oncology, Huashan Hospital Fudan University, Shanghai, China. ruofanhuang@fudan.edu.cn. 4. Department of Oncology, Huashan Hospital Fudan University, Shanghai, China. Xinli_zhou73@163.com.
Abstract
BACKGROUND: The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples from lung adenocarcinoma (LAC) patients with leptomeningeal metastases (LM). METHODS: Paired CSF cell free DNA (cfDNA), CSF cells, plasma and formalin-fixed and paraffin-embedded (FFPE) samples of primary tumors were collected from 29 LAC patients with LM to detect the mutations by different NGS pipelines. RESULTS: DNA libraries were generated successfully for 79 various samples in total for NGS sequencing, of which mutations were detected in 7 plasma samples (24.14%), 12 CSF cfDNA samples (66.67%), and 10 CSF cells (76.9%) samples. For the 26 patients with detected mutations, 8/26(30.77%) had mutations in plasma, which was significantly lower than that those from CSF cfDNA (12/15, 80.00%), CSF cells (10/11, 90.91%) and FFPE samples (13/17, 76.47%). When the input DNA of CSF cells was less than 20 ng, the cHOPE pipeline of NGS identified the most mutations for epidermal growth factor receptor (EGFR). CONCLUSIONS: NGS-based detection of mutations in cfDNA or cells from CSF provided more information than from plasma samples from LAC patients with LM. In addition, the cHOPE pipeline performed better than the other three NGS pipelines when input DNA from CSF cells was low.
BACKGROUND: The nucleic acid mutation status in intracranial metastasis is markedly significant clinically. The goal of the current study was to explore whether the tumor-associated mutations can be detected by different next-generation sequencing (NGS) pipelines in paired cerebrospinal fluid (CSF) and plasma samples from lung adenocarcinoma (LAC) patients with leptomeningeal metastases (LM). METHODS: Paired CSF cell free DNA (cfDNA), CSF cells, plasma and formalin-fixed and paraffin-embedded (FFPE) samples of primary tumors were collected from 29 LAC patients with LM to detect the mutations by different NGS pipelines. RESULTS: DNA libraries were generated successfully for 79 various samples in total for NGS sequencing, of which mutations were detected in 7 plasma samples (24.14%), 12 CSF cfDNA samples (66.67%), and 10 CSF cells (76.9%) samples. For the 26 patients with detected mutations, 8/26(30.77%) had mutations in plasma, which was significantly lower than that those from CSF cfDNA (12/15, 80.00%), CSF cells (10/11, 90.91%) and FFPE samples (13/17, 76.47%). When the input DNA of CSF cells was less than 20 ng, the cHOPE pipeline of NGS identified the most mutations for epidermal growth factor receptor (EGFR). CONCLUSIONS: NGS-based detection of mutations in cfDNA or cells from CSF provided more information than from plasma samples from LAC patients with LM. In addition, the cHOPE pipeline performed better than the other three NGS pipelines when input DNA from CSF cells was low.
Authors: Stepan M Esagian; Georgia Ι Grigoriadou; Ilias P Nikas; Vasileios Boikou; Peter M Sadow; Jae-Kyung Won; Konstantinos P Economopoulos Journal: J Cancer Res Clin Oncol Date: 2020-05-27 Impact factor: 4.553
Authors: Alicia Baumgartner; Natalia Stepien; Lisa Mayr; Sibylle Madlener; Christian Dorfer; Maria T Schmook; Tatjana Traub-Weidinger; Daniela Lötsch-Gojo; Dominik Kirchhofer; Dominik Reisinger; Cora Hedrich; Saleha Arshad; Stefan Irschik; Heidrun Boztug; Gernot Engstler; Marie Bernkopf; Fikret Rifatbegovic; Christoph Höller; Irene Slavc; Walter Berger; Leonhard Müllauer; Christine Haberler; Amedeo A Azizi; Andreas Peyrl; Johannes Gojo Journal: J Pers Med Date: 2021-04-12