Clinical next generation sequencing in cancer

      The use of massively parallel sequencing (MPS) (also known as next generation sequencing [NGS]) for analysis of DNA sequence alterations in malignancies has been driven by advances in our understanding of the genetic bases of cancer. Over the last decade, many different groups have shown that, while specific mutations in individual genes are characteristic of particular neoplasms, for most tumor types mutations in individual genes are not sufficient for development of a fully malignant phenotype. Instead mutations must be accumulated in a number of different oncogenes, tumor suppressor genes, and genes involved in cell cycle control, signaling, and metabolism (
      • Vogelstein B.
      • Papadopoulos N.
      • Velculescu V.E.
      • et al.
      Cancer genome landscapes.
      ,
      • Ley T.J.
      • Mardis E.R.
      • Ding L.
      • et al.
      DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
      ,
      • Ellis M.J.
      • Ding L.
      • Shen D.
      • et al.
      Whole-genome analysis informs breast cancer response to aromatase inhibition.
      ,
      • Berger M.F.
      • Hodis E.
      • Heffernan T.P.
      • et al.
      Melanoma genome sequencing reveals frequent PREX2 mutations.
      ,
      • Govindan R.
      • Ding L.
      • Griffith M.
      • et al.
      Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
      ). In addition, it has become apparent that the types of sequence changes involved in malignant transformation are also quite complicated. In general, the sequence changes can be grouped into four major categories, specifically single nucleotide variants (SNVs), small insertions and deletions (indels, usually from one to only several dozen base pairs long), copy number variants (CNVs, usually >1 kb long), and structural variants (SVs, including translocations, inversions, and large-scale deletions and duplications).
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