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A. Moreira

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    MINI 38 - Biology and Prognosis (ID 167)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      MINI38.02 - BAP1 Inactivation in Mesothelioma Is Highly Prevalent (ID 657)

      18:30 - 20:00  |  Author(s): A. Moreira

      • Abstract
      • Presentation
      • Slides

      Efforts to elucidate tumorigenic mutations in mesothelioma are essential to advance therapy. Prior efforts to characterize the molecular heterogeneity of this disease have been limited by sample condition and testing platforms. Herein, we describe efforts to prospectively test patients using next-generation sequencing with matched patient germline controls.

      Sequential mesothelioma patients were approached for consent to our IRB protocol NCT01775072 to perform MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), a comprehensive molecular profiling platform based on solution-phase exon capture and next generation sequencing to detect somatic genetic alterations in FFPE tumor specimens. MSK-IMPACT involves hybridization capture and deep sequencing of all protein-coding exons of 341 key cancer-associated genes, including all genes that are druggable by approved therapies or are targets of experimental therapies being investigated in clinical trials at MSKCC.

      51 patients with mesothelioma underwent MSK-IMPACT testing (see Table 1). 12 samples had low tumor content. Among 39 samples with reliable results, BAP1 was the most common alteration (46%). Another 3 samples had changes also thought to inactivate BAP1 (2 samples had gene copy number changes just below the cutoff for whole gene deletions and 1 had an inversion of LIMD-BAP1 thought to inactivate BAP1), making the incidence of BAP1 alterations possibly as high as 56%. In 4 samples with sufficient tumor content, no alterations were identified. Table 1

      N=39 (%)
      Gender M/F 26/13 (67/33)
      Primary site of disease * Pleural * Peritoneal * Testicular 32 (82) 6 (15) 1 (3)
      # identified alteration, average 3
      Alterations present in >6% * BAP1 * NF2 * CDKN2Ap16INK4A * SETD2 * CDKN2Ap14ARF * LATS1 * CREBBP * WT1 * CDKN2B * PI3KCA * PBRM1 * TP53 18 (46) 8 (21) 5 (13) 5 (13) 4 (10) 4 (10) 4 (10) 4 (10) 3 (8) 3 (8) 3 (8) 3 (8)

      Using MSK-IMPACT, BAP1 inactivation is the most common alteration. Other aberrations previously reported at high frequency were identified but albeit at lower frequencies (NF2 and p16, previously reported as 40% and 75% respectively). For multiple samples with deep coverage, no alterations were identified. The high incidence of BAP1 mutations in this systematic testing makes this pathway ideal for developing and testing targeted therapies.

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