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Artit Jinawat



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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-08 - Tumor Heterogeneity and Molecular Profile of NSCLC in Thai Population (ID 14016)

      12:00 - 13:30  |  Author(s): Artit Jinawat

      • Abstract
      • Slides

      Background

      Oncogenic driven mutation is the key to develop targeted therapy in lung cancer. Different ethnicity and tumor heterogeneity affect the prevalence of molecular alteration. This study aimed to explore the unique molecular profile of lung adenocarcinoma in Thai population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We studied 166 lung adenocarcinoma patients’ molecular profile using Next Generation Sequencing (NGS) on 45 genes lung cancer panel (Ion Torrent system). Variants from NGS with coverage of higher than 1000X and cut off at 2% alternate variant frequency were considered positive. We validated the positive mutation of EGFR, BRAF, and KRAS by Real- Time PCR using the Amoy DX kit.

      4c3880bb027f159e801041b1021e88e8 Result

      This study found 68%(113/166) of EGFR mutation, 9.6%(16/166) of BRAF V600E, 32.5% (54/166) of KRAS mutation, 9%(15/166) of MET exon14 splice site, 4.8% (8/166) AKT mutation (E17K), 2.4% (4/166) of ROS1 mutation, 0.6% (1/166) of PIK3CA mutation (H1047R), and 0.6% (1/166) of PTEN mutation. Furthermore, we also found 40 patients (24.1%) who had more than one mutation in each person. We further validated the positive results by Real-Time PCR. Thirteen patients were obtained tissue from different organs and some with different period of time. T790M usually develop later in EGFR-positive patients who failed 1st or 2nd generation EGFR-TKI. Two patients (patient 5&9) who had lung surgery different lobe in same operation, had different mutation in tissues and one patient (patient 13) who obtained tissue from lung and pleural effusion cell block in different period of time had totally different mutation (Table1).

      Table1 Tumor heterogeneity profile in lung cancer patients

      case

      Hetrogenety in different organ

      date obtained tissue

      Gene mutation

      EGFR

      KRAS

      ROS

      PTEN

      AKT

      MET

      BRAF

      1

      RLL lobectomy

      12-Jun-2012

      Exon 19 Deletion

      negative

      negative

      negative

      negative

      negative

      negative

      Right lung

      4-May-2016

      Exon 19 Deletion T790M

      negative

      negative

      negative

      negative

      negative

      negative

      2

      lymph node

      16-Mar-2017

      negative

      negative

      negative

      negative

      negative

      negative

      negative

      Bone

      9-Apr-2017

      negative

      negative

      negative

      negative

      negative

      negative

      negative

      3

      Right upper lung biopsy

      20-Jan-2016

      Exon 19 Deletion

      negative

      negative

      negative

      negative

      negative

      negative

      Lung biopsy

      31-Mar-2017

      T790M

      negative

      negative

      negative

      E17K

      negative

      negative

      4

      lymph node

      13-Jan-2016

      negative

      G12A

      negative

      negative

      negative

      negative

      negative

      skin

      17-Jan-2016

      negative

      G12V G12D

      negative

      negative

      negative

      negative

      negative

      left humerous

      30-Jun-2016

      negative

      G12V

      negative

      negative

      negative

      negative

      negative

      5

      RML lobectomy

      13-Nov-2013

      Exon 19 Deletion

      G13D

      negative

      negative

      negative

      negative

      negative

      LUL lobectomy

      14-May-2014

      negative

      G12D G13D

      negative

      R233*

      negative

      negative

      negative

      LUL lobectomy

      14-May-2014

      negative

      G12V G12D

      D2033N

      negative

      negative

      negative

      negative

      6

      Right pleura biopsy

      11-Jan-2016

      Exon 19 Deletion

      negative

      negative

      negative

      negative

      negative

      negative

      RUL biopsy

      1-Mar-2017

      Exon 19 Deletion

      negative

      negative

      negative

      negative

      negative

      negative

      7

      RUL biopsy

      28-Sep-2015

      L858R

      negative

      negative

      negative

      negative

      negative

      negative

      Left pleural fluid cell block

      27-Jun-2016

      negative

      negative

      negative

      negative

      negative

      negative

      negative

      8

      Right pleural fluid cell block

      25-Mar-2016

      Exon 19 Deletion

      negative

      negative

      negative

      negative

      negative

      negative

      Left pleural fluid cell block

      9-Dec-2016

      T790M

      negative

      negative

      negative

      negative

      negative

      negative

      9

      RML lobectomy

      14-Mar-2013

      negative

      G13S

      negative

      negative

      E17K

      negative

      negative

      RLL wedge resectionRLL lo

      30-Mar-2017

      G719A L861Q

      negative

      negative

      negative

      negative

      negative

      negative

      10

      RLL lobectomy

      26-Aug-2013

      negative

      G12C G12D

      negative

      negative

      negative

      negative

      negative

      Left lingular lobe segmental resection

      9-Oct-2014

      negative

      G12D

      negative

      negative

      negative

      negative

      negative

      LUL wedge resection

      11-Feb-2016

      negative

      G12D

      negative

      negative

      negative

      negative

      negative

      LUL lobectomy

      4-Jun-2017

      negative

      G12D

      negative

      negative

      negative

      negative

      negative

      LLL resection

      9-Oct-2014

      negative

      G12D

      negative

      negative

      negative

      negative

      negative

      11

      Right pleural cell block

      21-Jul-2014

      L858R

      negative

      negative

      negative

      negative

      c.3028G>A exon 14 splicing

      negative

      Ascites

      9-Jun-2017

      T790M L858R

      negative

      negative

      negative

      negative

      negative

      negative

      12

      LUL biopsy

      24-Feb-2015

      L858R

      negative

      negative

      negative

      negative

      negative

      V600E

      Lt lung biopsy

      8-Jul-2016

      L858R

      negative

      negative

      negative

      negative

      negative

      negative

      13

      RLL biopsy

      14-Oct-2015

      negative

      negative

      negative

      negative

      negative

      c.3028+1G>T exon 14 splicing

      negative

      pleural fluid cell block

      15-Nov-2016

      Exon 19 Deletion T790M

      negative

      negative

      negative

      negative

      negative

      negative

      8eea62084ca7e541d918e823422bd82e Conclusion

      Thai populations have unique molecular alteration compared to the other ethnicities, especially, higher of BRAF V600E and MET exon14 splice site. Our population also has high co-mutation prevalence. Tumor heterogeneity is needed to explore in the larger cohort.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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