Concordance of anaplastic lymphoma kinase (ALK) gene rearrangements between circulating tumor cells and tumor in non-small cell lung cancer
| Autor: | Man Chun Leong, Mei Kim Ang, Tony Kh. Lim, Chwee Teck Lim, Brendan Pang, Alvin Soon Tiong Lim, Angela Takano, Chye Ling Tan, Tse Hui Lim, Yong Wei Chua, Daniel Shao-Weng Tan, Wan-Teck Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Lung Neoplasms circulating tumor cells Adenocarcinoma 03 medical and health sciences 0302 clinical medicine Circulating tumor cell hemic and lymphatic diseases Carcinoma Non-Small-Cell Lung Biopsy molecular diagnosis medicine Biomarkers Tumor Anaplastic lymphoma kinase Humans Anaplastic Lymphoma Kinase Lung cancer In Situ Hybridization Fluorescence Aged Gene Rearrangement Crizotinib medicine.diagnostic_test ALK Gene Rearrangement business.industry ALK-gene rearrangement Receptor Protein-Tyrosine Kinases Gene rearrangement Middle Aged medicine.disease Neoplastic Cells Circulating Prognosis fluorescent in-situ hybridization lung cancer 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female business medicine.drug Research Paper Follow-Up Studies |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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 ALK-positive 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. |
| Databáze: | OpenAIRE |
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