Pathology

  • UI Pathology Offers First “Next Generation Sequencing” Test for Customized Cancer Care

     

    Molecular Pathology Group
    Front Row: Jon Pruessner, Connie Floerchinger, Jon Heusel
    Middle Row: Aaron Bossler, Deqin Ma
    Back Row: Ramakrishna Sompallae, Natalya Guseva

    Starting on October 24, the University of Iowa Department of Pathology implemented a new DNA sequencing test for Cancer Mutation Profiling and Interpretation. This is the first clinically validated massively parallel (‘next generation’) DNA sequencing test for cancer to be offered in Iowa. The assay looks at ‘hot spot’ regions of 50 cancer-related genes (see gene list below), including over 2,800 mutations listed in the catalogue of somatic mutations in cancer database (COSMIC1). The Cancer Mutation Profiling test provides valuable information about the genetic changes acquired by cancer cells—information that may help determine the cancer type, predict the behavior of the cancer (slow or fast-growing, metastatic spread, risk for recurrence or relapse), and predict the potential response to existing and emerging targeted therapies. On the implementation of the Cancer Mutation Profiling test—the first Next-Generation Sequencing (NGS) assay validated by the UI Health Care Molecular Pathology Lab, Jon Heusel, MD, PhD, states “This is an important step toward ‘precision medicine’ for patients of the Holden Comprehensive Cancer Center and the University of Iowa Health Care system. Bringing NGS technology to the clinical laboratory is emblematic of modern medicine, where we must rapidly integrate information on a massive scale, and then cooperate on the best management plan for each patient, every time. It is humbling—but also exciting.”

    The advantages of this next generation DNA sequencing test include the ability to survey 50 common cancer-related genes at once, saving valuable time and considerable costs compared to testing even 5-10 of the genes individually. Further, this test has the ability to see mutations at low levels, allowing assessment of specimens that contain mixtures of cancer and normal cells, as well as clonal heterogeneity within the cancer. Finally, the Cancer Mutation Profiling test may be performed using a very small amount of DNA—even from tissue that has already been formalin-fixed. This significantly expands the number of cases that can benefit from mutational profiling and related molecular testing. More information, better information, rapidly delivered…The Cancer Mutation Profiling and Interpretation Assay from University of Iowa Health Care is the beginning of a new approach in managing cancer. “We are excited to be offering this new technology in the war on cancer. I am proud of our team for their diligence and hard work in bringing this to fruition.” Aaron Bossler, MD, PhD, Molecular Pathology Laboratory Director.

    1. COSMIC-Catalogue of somatic mutations in cancer
    This test detects mutations from a relatively small amount of input human DNA (10 ng), and may be performed on fresh, frozen or formalin-fixed, paraffin-embedded (FFPE) tissues. The performance of this test has been extensively evaluated by the Molecular Pathology Laboratory. The limit of detection for single nucleotide substitutions is 5%, and 10% for deletions or insertions up to 25 bp. The assay cannot detect larger insertions, deletions, translocations, or other structural or copy number variations. The turn-around-time for this test is 21 days. At this time, certain restrictions on ordering the Cancer Mutation Profiling and Interpretation test in EPIC apply; please contact the Molecular Pathology Laboratory (384-9870), Dr. Aaron Bossler (384-9566) or Dr. Jon Heusel (356-8616) with inquiries.

    Cancer Mutation Profiling and Interpretation Assay
    List of Targeted Cancer Genes and Associated Hot Spot Exons

    Gene   Exons in Coverage Region*   Gene   Exons in Coverage Region*  
    ABL1   4, 6, 7   IDH2   4 (includes R140 and R172)  
    AKT1   3, 4, 6, 7   JAK2   14 (includes V617)  
    ALK   23, 25   JAK3   4, 13, 16  
    APC   14, 16, 17   KDR   6, 7, 11, 19, 21, 26, 27, 30  
    ATM   8, 9, 12, 17, 26, 34, 35, 36, 39,
     50, 54, 55, 56, 59, 61, 63
     
    KIT   2, 9, 10, 11, 13, 14, 15, 17, 18 (includes V559 and D816)  
    BRAF   11, 15 (includes V600)   KRAS   2, 3, 4 (includes codons 12, 13,
     & 61)
     
    CDH1   3, 8, 9   MET   2, 11, 14, 16, 19  
    CDKN2A    2   MLH1   11, 12, 13  
    CSFR1   7, 22   MPL   10 (includes S505 and W515)  
    CTNNB1   3   NOTCH1   26, 27, 34  
    EGFR   3, 7, 15, 18, 19, 20, 21   NPM1   12  
    ERBB2   19, 20, 21, 22, 23, 24   NRAS   2, 3, 4 (includes codons 12, 13,
     & 61)
     
    ERBB4   3, 4, 6, 7, 8, 9, 15, 23   PDGFRA   12, 14, 15, 18 (includes D842)  
    EZH2   15, 16   PIK3CA   2, 5, 7, 8, 10, 14, 19 21 (includes E542, E54 & H 1047  
    FBXW7   4, 5, 6, 7, 8, 9, 10, 11   PTEN   1, 3, 5, 6, 7, 8 (includes R130,
     R173, and R233)
     
    FGFR1   6, 7, 8, 9   PTPN11   3, 13  
    FGFR2   4, 5, 6, 7, 8, 9, 10, 11, 12   RB1   4, 6, 10, 11, 14, 17, 18, 20, 21, 22  
    FGFR3   7, 9, 12, 14, 16, 18   RET   10, 11, 13, 15, 16  
    FLT3   11, 14, 16, 20 (includes D835)   SMAD4   3, 4, 5, 6, 8, 9, 10, 11, 12  
    GNA11   5 (includes Q209, but not R183)   SMARCB1   2, 4, 5, 9  
    GNAQ   5 (includes Q209, but not R183)   SMO   3, 5, 6, 9, 11  
    GNAS   8, 9   SRC   14  
    HNF1A   3, 4   STK11   1, 4, 5, 6, 8  
    HRAS   2, 3 (includes codons 12, 13 & 61)   TP53   1, 2, 3, 4, 7  
    IDH1   4 (includes R132)   VHL   1, 3, 3  

    *This assay does not provide full-length coverage for the listed exons; a detailed list of the genomic positions defining each of 207 amplicons is available upon request.