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https://doi.org/10.18632/oncotarget.8136
Title: | Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer | Authors: | Tan, Chye Ling Lim, Tse Hui Lim, Tony KH Tan, Daniel Shao-Weng Chua, Yong Wei Ang, Mei Kim Pang, Brendan Lim, Chwee Teck Takano, Angela Lim, Alvin Soon-Tiong Leong, Man Chun Lim, Wan-Teck |
Keywords: | Science & Technology Life Sciences & Biomedicine Oncology Cell Biology ALK-gene rearrangement circulating tumor cells fluorescent in-situ hybridization lung cancer molecular diagnosis EGFR MUTATIONS ADENOCARCINOMA METASTASIS INHIBITORS EML4-ALK FEATURES BIOPSY IMPACT DETECT TISSUE |
Issue Date: | 26-Apr-2016 | Publisher: | IMPACT JOURNALS LLC | Citation: | Tan, Chye Ling, Lim, Tse Hui, Lim, Tony KH, Tan, Daniel Shao-Weng, Chua, Yong Wei, Ang, Mei Kim, Pang, Brendan, Lim, Chwee Teck, Takano, Angela, Lim, Alvin Soon-Tiong, Leong, Man Chun, Lim, Wan-Teck (2016-04-26). Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer. ONCOTARGET 7 (17) : 23251-23262. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.8136 | Abstract: | Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) is routinely evaluated by fluorescent in-situ hybridization (FISH) testing on biopsy tissues. Testing can be challenging however, when suitable tissue samples are unavailable. We examined the relevance of circulating tumor cells (CTC) as a surrogate for biopsy-based FISH testing. We assessed paired tumor and CTC samples from patients with ALK rearranged lung cancer (n = 14), ALK-negative lung cancer (n = 12), and healthy controls (n = 5) to derive discriminant CTC counts, and to compare ALK rearrangement patterns. Blood samples were enriched for CTCs to be used for ALK FISH testing. ALK-positive CTCs counts were higher in ALKpositive NSCLC patients (3-15 cells/1.88 mL of blood) compared with ALK-negative NSCLC patients and healthy donors (0-2 cells/1.88 mL of blood). The latter range was validated as the 'false positive' cutoff for ALK FISH testing of CTCs. ALK FISH signal patterns observed on tumor biopsies were recapitulated in CTCs in all cases. Sequential CTC counts in an index case of lung cancer with no evaluable tumor tissue treated with crizotinib showed six, three and eleven ALK-positive CTCs per 1.88 mL blood at baseline, partial response and post-progression time points, respectively. Furthermore, ALK FISH rearrangement suggestive of gene copy number increase was observed in CTCs following progression. Recapitulation of ALK rearrangement patterns in the tumor on CTCs, suggested that CTCs might be used to complement tissue-based ALK testing in NSCLC to guide ALK-targeted therapy when suitable tissue biopsy samples are unavailable for testing. | Source Title: | ONCOTARGET | URI: | https://scholarbank.nus.edu.sg/handle/10635/218637 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.8136 |
Appears in Collections: | Elements Staff Publications |
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