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Å. Helland

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    MO16 - Prognostic and Predictive Biomarkers IV (ID 97)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO16.07 - Higher frequency of genetic aberrations in KRAS- than in EGFR-mutated NSCLCs. A next-generation sequencing study on 96 samples. (ID 1094)

      16:15 - 17:45  |  Author(s): Å. Helland

      • Abstract
      • Presentation
      • Slides

      Genetic subtyping is increasingly being clinically relevant in NSCLC, and the search for novel targetable driver mutations is warranted. We intended to study the frequency and types of a vast number of potential druggable genetic aberrations in a large cohort of non-small cell lung cancers of all major histological subtypes. Herein we report the first findings.

      Blood samples and tumor tissue was obtained from 96 operated early stage lung cancer patients admitted to Oslo University Hospital-Rikshospitalet in the period 2006-2011. Tissue was taken from the excised tumours, snap frozen in liquid nitrogen in the operation room, and stored at -80[o]C until DNA isolation. The tumor cell content in the specimens was found to be more than 70% in most samples. DNA was isolated from both tumor and corresponding blood sample according to standard procedures. High-throughput sequencing was performed using the SureSelect Human Kinome kit (Agilent Technologies), with capture probes that target 3.2 Mb of the human genome and include exons for all known kinases, select cancer-specific genes and their associated UTRs, in total 612 genes. The derived sequence reads were analyzed based on a pipeline including calling variations, somatic mutations, DNA copy number changes, indels and genomic rearrangements, as well as functional annotations.

      Tissues from 48 females and 48 males were analyzed; 73 adenocarcinomas, 21 squamous cell carcinomas and 2 large cell carcinomas. 55 patients were in stage I, 27 in II and 14 in stage III. 13 patients were never-smokers. 25 samples harbored a KRAS-mutation and 10 an EGFR mutation. The number of mutated genes per sample varied from 1 to 81. The median number of mutated genes was 14 in the overall cohort, 15 in the EGFR wildtype/KRAS wildtype tumors, 17 in KRAS- mutated patients, 5 in the EGFR-mutated group and 6 in the never-smoking patients (of whom 4 patients were EGFR-mutated).Figure 1

      KRAS-mutated tumors contain the same amount of genetic aberrations as in wild-type tumors, whereas EGFR-mutated tumors show a much lower number of mutations per tumor. Never-smokers harbor a low number of mutations independent of EGFR-mutation status. Novel driver mutations are probably found in samples with low numbers of mutations.

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