Tumour evolution inferred by single-cell sequencing
Nicholas Navin,Jude Kendall,Jennifer Troge,Peter Andrews,Linda Rodgers,Jeanne McIndoo,Kerry Cook,Asya Stepansky,Dan Levy,Diane Esposito,Lakshmi Muthuswamy,Alexander Krasnitz,W. Richard McCombie,James W. Hicks,Michael Wigler +14 more
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TLDR
It is shown that with flow-sorted nuclei, whole genome amplification and next generation sequencing the authors can accurately quantify genomic copy number within an individual nucleus and indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.Abstract:
Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.read more
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Identification of PLX4032-resistance mechanisms and implications for novel RAF inhibitors
Jaehyuk Choi,Sean Landrette,Tiffany Wang,Perry Evans,Antonella Bacchiocchi,Robert D. Bjornson,Elaine Cheng,Amy L. Stiegler,Symon Gathiaka,Orlando Acevedo,Titus J. Boggon,Michael Krauthammer,Ruth Halaban,Tian Xu,Tian Xu +14 more
TL;DR: It is demonstrated that the PLX4032‐resistant melanoma cells are sensitive to novel, next‐generation BRAF inhibitors, especially the ‘paradox‐blocker’ PLX8394, supporting its use in clinical trials for treatment of melanoma patients with BRAF‐mutations.
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Progress in the clinical detection of heterogeneity in breast cancer.
TL;DR: This study reviews how the understanding of tumor heterogeneity in breast cancer evolved, and further summarizes recent advances in the detection and monitoring of this heterogeneity in patients with breast cancer.
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Computing tumor trees from single cells
Alexander Davis,Nicholas Navin +1 more
TL;DR: Computational methods have been developed to reconstruct evolutionary lineages from tumors using single-cell genomic data, and the resulting tumor trees have important applications in cancer research and clinical oncology.
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Emerging roles of the tumor-associated stroma in promoting tumor metastasis
TL;DR: The stroma in human carcinomas consists of extracellular matrix and various types of non-carcinoma cells, mainly leukocytes, endothelial cells, fibroblasts, myofibroblast and bone marrow-derived progenitors, which actively supports tumor growth by stimulating neo-angiogenesis, as well as proliferation and invasion of apposed carcinoma cells.
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Methods, challenges and potentials of single cell RNA-seq
TL;DR: The current single cell RNA-seq efforts are reviewed and experimental protocols, challenges, challenges and potentials are discussed.
References
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