Fusion Genes and their Detection through Next Generation Sequencing in Malignant Hematological Disease and Solid Tumors

Abstract

Fusion genes are neoplasia-associated mutations, which play a particularly significant role in tumorgenesis and exhibit great importance for clinical applications in malignant hematological diseases and solid tumors. Simultaneously with copy number variants (CNVs), gene fusions are resulting from balanced and unbalanced chromosomal rearrangements. Thus, understanding the mutagenesis and instability of CNV, as well as the underlying molecular mechanisms of chromosomal rearrangements will improve our comprehension of gene fusions. Recently, next generation sequencing (NGS), especially transcriptome sequencing or RNA-Sequencing (RNA-seq), has become a very useful tool to identify gene alterations in cancer and a powerful approach for investigating the tumorgenesis. However, we are still facing with the challenge of minimizing false positives in results of RNA-seq. Whole-genome sequencing (WGS) is also used for the fusion gene detection, which provides us a more comprehensive and integrative way to detect structural variants. WGS may correct the false-negative results from RNA-seq. Additionally; many computational tools with more sensitivity and specificity have been developed for the detection of fusion transcripts from NGS datas. In the future, multi-omics analysis, third-generation sequencing and liquid-biopsy technique all provide opportunities to comprehensively interpret gene fusions and understand the biology of cancer genomes.

RNA Biomarkers: Diagnostic and Prognostic Potentials and Recent Developments of Electrochemical Biosensors

“…Apart from BCR‐ABL, several other fusion mRNAs (e.g., TMPRSS2‐ERG) have attracted significant interest as cancer biomarkers due to their role in cancer development and high specificity (Mertens 2015) . Fusion mRNA is transcribed from fusion gene as the product of chromosomal rearrangements such as translocations, insertions, inversions, and interstitial deletions where two genes from each side of chromosomal breakpoint may fuse together . In addition, the coding sequences in one gene can be juxtaposed with the regulatory sequences of another gene to form the fusion gene .…”

“…The method showed excellent specificity in detecting TMPRSS2: ERG mRNA while a negative control cell line (TMPRSS2: ERG fusion gene absent) was used. Until now, the most preferable approach for identifying cancer associated fusion transcripts is the next‐generation sequencing (NGS), especially RNA‐seq . However, the detection of fusion mRNA by RNA‐seq has been limited by the resultant false‐positives response .…”