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Hirsh Koyi



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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.07 - A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer (ID 13145)

      15:55 - 16:00  |  Author(s): Hirsh Koyi

      • Abstract
      • Presentation
      • Slides

      Background

      Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients’ medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].

      4c3880bb027f159e801041b1021e88e8 Result

      In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.

      8eea62084ca7e541d918e823422bd82e Conclusion

      SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.

      References

      1. http://www.cancercentrum.se/vast/cancerdiagnoser/lunga-och-lungsack/kvalitetsregister

      2. Staaf J, Jönsson G, Jönsson M, Karlsson A, Isaksson S, Salomonsson A,Pettersson HM, Soller M, Ewers SB, Johansson L, Jönsson P, Planck M. Relation between smoking history and gene expression profiles in lung adenocarcinomas. BMC Med Genomics. 2012 Jun 7;5:22.

      3. Karlsson A, Ringnér M, Lauss M, Botling J, Micke P, Planck M, Staaf J. Genomic and transcriptional alterations in lung adenocarcinoma in relation to smoking history. Clin Cancer Res. 2014 Sep 15;20(18):4912-24.

      4. Lindquist KE, Karlsson A, Levéen P, Brunnström H, Reuterswärd C, Holm K, Jönsson M, Annersten K, Rosengren F, Jirström K, Kosieradzki J, Ek L, Borg Å, Planck M, Jönsson G, Staaf J. Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer. Oncotarget. 2017 May 23;8(21):34796-34810.

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