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Rearranged EML4-ALK...
Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer
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- Nilsson, R. Jonas A. (author)
- Umeå universitet,Onkologi,Cancer Center Amsterdam, Department of Neurosurgery, VU University Medical Center, Amsterdam ; ThromboDx B.V., Amsterdam
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Karachaliou, Niki (author)
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Berenguer, Jordi (author)
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Gimenez-Capitan, Ana (author)
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Schellen, Pepijn (author)
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Teixido, Cristina (author)
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Tannous, Jihane (author)
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Kuiper, Justine L. (author)
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Drees, Esther (author)
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Grabowska, Magda (author)
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van Keulen, Marte (author)
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Heideman, Danielle A. M. (author)
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Thunnissen, Erik (author)
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Dingemans, Anne-Marie C. (author)
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Viteri, Santiago (author)
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Tannous, Bakhos A. (author)
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Drozdowskyj, Ana (author)
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Rosell, Rafael (author)
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Smit, Egbert F. (author)
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Wurdinger, Thomas (author)
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(creator_code:org_t)
- 2015-11-02
- 2016
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 1066-1075
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https://umu.diva-por... (primary) (Raw object)
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Abstract
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- Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- diagnostics
- NSCLC
- liquid biopsies
- platelets
- EML4-ALK
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Nilsson, R. Jona ...
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Karachaliou, Nik ...
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Berenguer, Jordi
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Gimenez-Capitan, ...
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Schellen, Pepijn
-
Teixido, Cristin ...
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show more...
-
Tannous, Jihane
-
Kuiper, Justine ...
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Drees, Esther
-
Grabowska, Magda
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van Keulen, Mart ...
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Heideman, Daniel ...
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Thunnissen, Erik
-
Dingemans, Anne- ...
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Viteri, Santiago
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Tannous, Bakhos ...
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Drozdowskyj, Ana
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Rosell, Rafael
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Smit, Egbert F.
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Wurdinger, Thoma ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Oncotarget
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Umeå University