التفاصيل البيبلوغرافية
| العنوان: |
Whole-genome sequencing of single circulating tumor cells from neuroendocrine neoplasms. |
| المؤلفون: |
Childs, Alexa, Steele, Christopher D., Vesely, Clare, Rizzo, Francesca M., Ensell, Leah, Lowe, Helen, Dhami, Pawan, Vaikkinen, Heli, Tu Vinh Luong, Conde, Lucia, Herrero, Javier, Caplin, Martyn, Toumpanakis, Christos, Thirlwell, Christina, Hartley, John A., Pillay, Nischalan, Meyer, Tim |
| المصدر: |
Endocrine-Related Cancer; Sep2021, Vol. 28 Issue 9, p631-644, 14p |
| مصطلحات موضوعية: |
NUCLEOTIDE sequencing, CIRCULATING tumor DNA, NEUROENDOCRINE cells, LEUCOCYTES, DRUG target, TUMORS |
| مستخلص: |
Single-cell profiling of circulating tumor cells (CTCs) as part of a minimally invasive liquid biopsy presents an opportunity to characterize and monitor tumor heterogeneity and evolution in individual patients. In this study, we aimed to compare single-cell copy number variation (CNV) data with tissue and define the degree of intra- and inter-patient genomic heterogeneity. We performed next-generation sequencing (NGS) whole-genome CNV analysis of 125 single CTCs derived from seven patients wit h neuroendocrine neoplasms (NEN) alongside matched white blood cells (WBC), formalin-fixed paraffinembedded (FFPE), and fresh frozen (FF) samples. CTC CNV profiling demonstrated recurrent chromosomal alterations in previously reported NEN copy number hotspots, including the prognostically relevant loss of chromosome 18. Unsupervised hierarchical clustering revealed CTCs with distinct clonal lineages as well as significant intra- and interpatient genomic heterogeneity, including subclonal alterations not detectable by bulk analysis and previously unreported in NEN. Notably, we also demonstrated the presence of genomically distinct CTCs according to the enrichment strategy utilized (EpCAM-dependent vs size-based). This work has significant implications for the identification of therapeutic targets, tracking of evolutionary change, and the implementation of CTC-biomarkers in cancer. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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