Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing

Yu, Chang; Yu, Jun; Yao, Xiaotian; Wu, William; Lü, Youyong; Tang, Senwei; Li, Xiangchun; Bao, Li; Li, Xiaoxing; Hou, Yong; Wu, Renhua; Jian, Min; Chen, Ruoyan; Zhang, Fan; Xu, Lixia; Fan, Fan; He, Jun; Liang, Qiaoyi; Wang, Hongyi; Hu, Xueda; He, Minghui; Zhang, Xiang; Zheng, Hancheng; Li, Qibin; Wu, Huawei; Chen, Yan; Xu, Yu; Zhu, Shida; Xu, Xun; Yang, Huanming; Wang, Jian; Zhang, Xiuqing; Sung, Joseph J.Y.; Li, Yingrui; Wang, Jun

doi:10.1038/cr.2014.43

Cited by 120 publications

(107 citation statements)

References 24 publications

(31 reference statements)

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…In recent years, a large number of studies have been reported using single cell analysis to analyze individual tumor cells isolated from breast cancer (Navin et al, 2011; Deng et al, 2014; Wang et al, 2014; Eirew et al, 2015), colon cancer (Zong et al, 2012; Yu et al, 2014), pancreatic adenocarcinomas (Ruiz et al, 2011), muscle-invasive bladder cancer (Li et al, 2012b), intestinal cancer (Grün et al, 2015), lung adenocarcinoma cancer (Kim et al, 2015), renal cell carcinoma (Gerlinger et al, 2012; Li et al, 2012b), and acute myeloid leukemia (Ding et al, 2012; Hughes et al, 2014; Paguirigan et al, 2015). For example, Navin and colleagues investigated copy number variation in single tumor cells using DOP WGA followed by DNA sequencing to determine cell population structure and tumor evolution patterns in a single breast tumor (Navin et al, 2011).…”

Section: Application Of Single Cell Analysismentioning

confidence: 99%

Single Cell Isolation and Analysis

Zhang

Xin

et al. 2016

Front. Cell Dev. Biol.

299

244

View full text Add to dashboard Cite

Individual cell heterogeneity within a population can be critical to its peculiar function and fate. Subpopulations studies with mixed mutants and wild types may not be as informative regarding which cell responds to which drugs or clinical treatments. Cell to cell differences in RNA transcripts and protein expression can be key to answering questions in cancer, neurobiology, stem cell biology, immunology, and developmental biology. Conventional cell-based assays mainly analyze the average responses from a population of cells, without regarding individual cell phenotypes. To better understand the variations from cell to cell, scientists need to use single cell analyses to provide more detailed information for therapeutic decision making in precision medicine. In this review, we focus on the recent developments in single cell isolation and analysis, which include technologies, analyses and main applications. Here, we summarize the historical background, limitations, applications, and potential of single cell isolation technologies.

show abstract

Section: Application Of Single Cell Analysismentioning

confidence: 99%

Single Cell Isolation and Analysis

Zhang

Xin

et al. 2016

Front. Cell Dev. Biol.

299

244

View full text Add to dashboard Cite

show abstract

“…In gastric cancer cases, PABPC1 has been found to be an oncoprotein 62 and observed to exert carcinogenesis. In colon cancer mutations in PABPC1 have been found in minor tumor clones 63 . Genomic correlates of immune-cell infiltrates in CRC have found the existence of significantly mutated CRC genes 64 .…”

Section: Dicationmentioning

confidence: 99%

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

View full text Add to dashboard Cite

WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

show abstract

“…Recently, a series of exciting studies utilizing SCS in some major cancers were reported, such as breast cancer (16,47), colon cancer (18,67), muscle-invasive bladder cancer (68), intestinal cancer (69), lung adenocarcinoma cancer (27), kidney tumor (70), and acute myeloid leukemia (71,72). These studies made unprecedented progress in understanding carcinogenesis, progression, metastasis, and drug resistance.…”

Section: Preliminary Applications Have Led To Exciting Discoveriesmentioning

confidence: 99%

“…Interestingly, some genes discovered by SCS exhibited a high frequency of mutations at the single-cell level, but low prevalence in the tumor mass (16,67). Some genes exhibited specific alternative splicing of exon isoforms in different single-cell transcriptomes (30).…”

Section: Preliminary Applications Have Led To Exciting Discoveriesmentioning

confidence: 99%

Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects

et al. 2016

View full text Add to dashboard Cite

Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing.

show abstract

Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing

Cited by 120 publications

References 24 publications

Single Cell Isolation and Analysis

Single Cell Isolation and Analysis

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects

Contact Info

Product

Resources

About