Next Generation Genome Sequencing (NGS)

NGS has been used to identify rare variants in patient cohorts and to classify genomes of individual patients.1 In whole-genome sequencing2:

  • DNA is isolated from a patient
  • The whole sequence is determined
  • A bioinformatics computer system compares the patient’s sequence to a reference sequence and then:
    • Notes any differences
    • Determines which differences could hold clinical relevance

NGS has been useful in sequencing a large number of novel abnormalities in cancer genomes. NGS has discovered major driver mutations in both solid and hematopoietic malignancies, such as DNMT3A (inactivating DNA methylation) in acute myeloid leukemia (AML).2

With increased speed and decreased costs, NGS has the potential to improve medical care by making possible widespread evaluation of patients’ genomes in clinical settings.2

For some patients with malignant neoplasms, NGS can improve tumor classification, diagnosis, and management. However, many challenges remain, including2:

  • The storage and interpretation of vast amounts of sequence data
  • Training physicians
  • Slow turnaround time
  • Healthcare professionals whose knowledge of genetics may be insufficient
  • Effective genetic counseling and communication of results to patients with germline mutations
  • Establishing standards for the appropriate use of the technology

Examples of NGS platforms: Roche/454, Illumina/Solexa, and Life Technologies/SOLiD. Newer technologies, such as fluorescence resonance energy transfer (FRET), are in development.1

References: 1. Xuan J, Yu Y, Qin T, Guo L, Shi L. Next-generation sequencing in the clinic: promises and challenges. Cancer Lett. 2013;340(2):284-295. 2. Taber KAJ, Dickinson BD, Wilson M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern Med. 2014;174(2):275-280.