Academic Journal
L1 Retrotransposon heterogeneity in ovarian tumor cell evolution
| العنوان: | L1 Retrotransposon heterogeneity in ovarian tumor cell evolution |
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| المؤلفون: | Nguyen, Thu H.M., Carreira, Patricia E., Sánchez-Luque, Francisco J., Schauer, Stephanie N., Fagg, Allister C., Richardson, Sandra R., Davies, Claire M., Jesuadian, J. Samuel, Kempen, Marie-Jeanne H.C., Troskie, Robin-Lee, James, Cini, Beaven, Elizabeth A., Wallis, Tristan P., Coward, Jermaine I.G., Chetty, Naven P., Crandon, Alexander J., Venter, Deon J., Armes, Jane E., Perrin, Lewis C., Hooper, John D., Ewing, Adam D., Upton, Kyle R., Faulkner, Geoffrey J. |
| المساهمون: | University of Queensland, European Commission, Australian Research Council, National Health and Medical Research Council (Australia) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2018 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | Ovarian cancer, Retrotransposon, LINE-1, L1, Chemoresistance |
| الوصف: | LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity. ; This study was supported by an Australian Postgraduate Award to T.H.M.N., a University of Queensland Postdoctoral Research Fellowship to K.R.U., an Australian Research Council Discovery Early Career Researcher Award (DECRA) fellowship (DE150101117) to A.D.E., and the European Union (EU) Seventh Framework Programme (FP7) under grant agreement PIOF-GA-2013-623324 to F.J.S.-L. G.J.F. acknowledges support from the Mater Foundation, a CSL Centenary Fellowship, National Health and Medical Research Council (NHMRC) project grants (GNT1042449, GNT1045991, GNT1067983, GNT1068789, and GNT1106206), and the EU FP7 under grant agreement 259743. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/EC/FP7/623324; The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1016/j.celrep.2018.05.090; https://doi.org/10.1016/j.celrep.2018.05.090; No; http://hdl.handle.net/10261/376198 |
| DOI: | 10.1016/j.celrep.2018.05.090 |
| الاتاحة: | http://hdl.handle.net/10261/376198 https://doi.org/10.1016/j.celrep.2018.05.090 |
| Rights: | open |
| رقم الانضمام: | edsbas.1C7C14F0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2018.05.090 |
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