In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 5402-5402
Abstract:
We performed RNA sequencing of single cells derived from a high grade serous ovarian cancer (HGSOC) specimen to determine the extent of heterogeneity and to determine if it was feasible to identify cancer stem cells or gene expression signatures of chemo resistance. To perform RNA sequencing we enzymatically digested a fresh specimen from an HGSOC derived from the ovary. Immune cells were depleted by flow cytometry and single cell sequencing was performed using the Fluidigm C1 chip in tandem with Illumina HiSeq 2500 sequencing. Multiple bioinformatics tools were used to identify subgroups and activated pathways. Immunohistochemistry was performed on an adjacent tumor section to analyze markers of epithelium, stroma and stem cells. We found that gene expression patterns in single cells could be used to separate cells into stroma-like and epithelial-like groups. Gene set enrichment analysis identified proliferative genesets (oxidative phosphorylation and MYC targets) associated with the epithelial-like cells while epithelial-to-mesenchymal-transition (EMT) genes associated with the stroma-like cells. Neither group was significantly associated with genesets derived from chemo-resistant cells. Using known marker analysis, we could identify a small percentage of cells that expressed ovarian cancer stem cell markers and we could group cells into functional categories. Using four molecular subtypes established from large-scale bulk sequencing studies we show that single cells from a single patient are heterogeneous and each molecular subtype is represented. In conclusion, we show the feasibility of performing single cell sequencing on an epithelial ovarian cancer and reveal a heterogeneous population of cells. Expanding these findings to a larger cohort of patients could allow for identification of targetable sub-populations of cells that were previously undetectable in studies that use bulk samples to interrogate the transcriptome and genome of ovarian cancer patients. Citation Format: Timothy K. Starr, Boris Winterhoff, Makayla Maile, Kenneth Beckman, Jerry Daniel, Melissa Geller, Martina Bazzaro, Molly Klein, Raffaele Hellweg, Juan Abrahante, Amit K. Mitra, Atilla Sebe, Sally A. Mullany. Single cell sequencing of high grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5402. doi:10.1158/1538-7445.AM2017-5402
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-5402
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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