![]() ![]() Nevertheless, great advancements have recently been made towards addressing these two hurdles. However, due to the high false positive rate and the low detection sensitivity, the diagnostic potential of these discoveries has not been fully realized in a clinical setting. Using bulk RNAseq, numerous novel gene fusions have been discovered, many of which can be directly beneficial as FDA approved drugs or offer new therapeutic opportunities 14, 15, 16, 17. Some recurrent fusion genes can be used as a diagnostic tool, such as the RUNX1–RUNX1T1 fusion for diagnosis of acute myeloid leukemia 12, while others may be considered as prognostic biomarkers like TMPRSS2–ERG fusion in prostate cancer 13. Fusion genes are well documented as major cancer drivers. If this selection strategy is applicable in other tumor types, more biomarker signatures can be readily translated into clinical practice.Īnother area subject to intensive clinical research is gene fusion discoveries. Such a transcriptomic signature minimizes sampling bias and offers robust prognostic performance in NSCLC survival. These genes “encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains” 11. By analyzing multiple RNAseq data from lung cancer patients, the team found that genes with homogeneous expression within individual tumors, despite high inter tumor variability, have significantly better prognostic potential. A recent study provided a promising solution to tackle this issue through a novel strategy for biomarker selection 11. One of the main reasons for the poor performance across independent tumor patients is sampling bias inherent to intra-tumor heterogeneity 10. However, only a few such signature panels have been successfully translated into clinical practice due to low reproducibility. Numerous RNAseq-based signatures have been developed and validated across many major tumor types 5, 6, 7, 8, 9. The most informative area is the biomarker discoveries for cancer diagnosis, prognosis, and prediction. The translational research targeted for clinical oncology is primarily in two areas. 1).īulk RNAseq has broad utilities in cancer classification, biomarker and gene fusion discoveries, disease diagnosis, and optimizing therapeutic treatment. This type of bulk RNAseq normally sequences rRNA-depleted libraries for more comprehensive information (Fig. The less routinely used type is paired end longer sequencing aimed at additional knowledge on alternative splicing, point mutations, novel transcripts, long non-coding RNAs and gene fusions. This type of sequencing is simple and cost effective, largely focused on mRNA only. By sequencing type, the most frequently used bulk RNAseq is a single end short sequencing focused on differentially expressed genes to understand molecular mechanisms implicated in various stage of tumorigenesis. Instead, we will highlight the bottlenecks of its clinical translation and the recent progresses toward their solutions.īy RNA species, bulk RNAseq involves sequencing two types of libraries: mRNA-only library and whole transcriptome library that includes all RNA species except for rRNA. This section does not intend to discuss either technologies or its applications in details. Its diverse translational research and potential clinical applications have been well reviewed in the past 2, 3, 4. Since the first EST library was sequenced using Roche 454 sequencer in 2007 1, bulk RNAseq has become the most valuable and extensively used tool in understanding cancer biology. Therefore, RNAseq is a powerful tool for understanding the molecular mechanisms of cancer development and developing novel strategies for cancer prevention and treatment. Different gene expression profiles may reflect different cancer subtypes, the stage of cancer development or tumor microenvironment 2, 3, 4. Aberrant activation of cell growth signaling pathways and/or transcription factors could lead to high-level expression of genes associated with tumor development and progression. In addition to the mutation of tumor suppressor genes and oncogenes, gene expression could be overactivated or epigenetically silenced which could lead to uncontrolled tumor cell growth and proliferation. Abnormal expression of RNA is frequently associated with human cancer initiation, development, progression and metastasis. RNA transcription and stability are tightly regulated in response to physiological and pathological stimuli 1. Ribonucleic acid (RNA) has multiple forms and plays a critical role in cell growth and differentiation.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |