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Eunjoo Hwang



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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • 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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      P3.13-29 - Patient-Derived Xenograft Models(PDX) of Lung Squamous Cell Carcinoma(SCC) for Preclinical Studies (ID 14278)

      12:00 - 13:30  |  Author(s): Eunjoo Hwang

      • Abstract
      • Slides

      Background

      Non-small cell lung cancer is the most prevalent type of lung cancer, and one of its subtype, squamous cell carcinoma has limited targeted therapeutic options in comparison with adenocarcinoma. For this reason, we established the patient-derived xenograft models of primary lung cancer and then focused on the SCC PDX models to be used for the discovery of target mutations through the molecular profiling of lung tumors and their association of therapeutic responses

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PDX models were established using the tissues of patients who underwent surgery as primary lung cancer at Samsung Medical Center during the period between October, 2014 and September, 2017. Briefly, tumor tissues from patients were subcutaneously engrafted and passaged two more times in NOD-scid-IL2RĪ³null mouse. Then we are analyzing histological characteristics and molecular profiles of established SCC PDX by whole exome sequencing and whole transcriptome sequencing.

      4c3880bb027f159e801041b1021e88e8 Result
      Mutation profiles of squamous cell carcinoma Patient Tumors and their PDX models

      Patient tumor

      PDX

      ID

      Gene

      Mutation

      Frequency

      Gene

      Mutation

      Frequency

      PDL-040

      HRAS

      JAK1

      PTEN

      TP53

      GNAQ

      U2AF1

      G13V

      N136fs

      -78fs

      Y236C

      T96S/M59L

      G167C

      1.000

      0.397

      0.488

      1.000

      0.143/0.080

      0.080

      PDL-041

      CTNNA2

      FRG1

      M672I

      C159Y

      0.278

      0.042

      PDL-089

      EP300

      AMER1

      RB1

      EP300

      AMER1

      RB1

      0.473

      0.576

      0.500

      AMER1

      RB1

      EP300

      R142K

      I425fs

      G438V

      0.851

      0.472

      0.479

      PDX-073

      PDX-079

      DNMT3A

      BRAF

      TP53

      FRG1

      F571L

      V600E

      R249S

      Q137K

      0.606

      0.524

      0.571

      0.521

      BRAF

      TP53

      FRG1

      DNMT3A

      V600E

      R249S

      Q137K

      F571L

      0.377

      1.000

      0.026

      0.444

      PDX-100

      DDR2

      BRAF

      GNAS

      TP53

      E757D

      G469A

      Q286P

      156_157RV>L

      0.484

      0.388

      0.583

      0.671

      BRAF

      DDR2

      TP53

      GNAS

      G469A

      E757D

      156_157RV>L

      Q286P

      0.941

      0.212

      0.500

      0.180

      PDX-114

      PDX-186

      KEAP1

      PIK3R1

      L281M

      M200fs

      1.000

      0.464

      PDX-190

      PDX-205

      PDX-207

      TP53

      ATRX

      C176F

      S1944R

      0.617

      0.537

      TP53

      C176F

      1.000

      PDX-231

      MET

      STK11

      KEAP1

      RPSAP58

      GNAS

      L829V

      D115N

      G333C

      Q113H

      V57M

      0.494

      0.410

      0.551

      0.426

      0.488

      KEAP1

      MET

      STK11

      GNAS

      RPSAP58

      SMO

      G333C

      L829V

      D115N

      V57M

      Q113H

      R138L

      1.000

      0.485

      1.000

      0.318

      1.000

      0.400

      PDX-252

      HLA-A

      HLA-A

      HLA-A

      HLA-A

      HLA-A

      HLA-A

      TSC1

      FRG1

      ATRX

      EEF1B2

      R38W

      G80R

      A114D

      S129P

      T187P

      T187R

      S487C

      Q137K

      Q929E

      R122H

      0.500

      0.267

      0.617

      0.611

      0.091

      0.231

      0.293

      0.026

      0.870

      0.227

      PDX-271

      TSC1

      KDR

      M322T

      V297I

      0.357

      0.300

      PDX-302

      JAK1

      TP53

      E667Q

      N268I

      0.514

      0.488

      PDX-318

      ARID1A

      NF1

      TP53

      FRG1

      SMO

      SOX17

      TRRAP

      H203Q

      R2556T

      LRKKGEPHH289fs

      A151G

      F332fs

      R147L

      A598V

      0.125

      0.168

      0.472

      0.048

      0.456

      0.200

      0.349

      PDX-364

      TSC2

      T927I

      0.575

      PDX-366

      KDR

      TP53

      NOTCH1

      FRG1

      A1103D

      V173L

      L107F

      Q137K

      0.494

      0.609

      0.600

      0.496

      NOTCH1

      TP53

      FRG1

      CHD4

      KDR

      L107F

      V173L

      Q137K

      R1825L

      A1103D

      0.160

      1.000

      0.035

      0.061

      0.270

      PDX-372

      CDKN2A

      TP53

      D33H

      A161fs

      0.377

      0.534

      CDKN2A

      TP53

      D33H

      A161fs

      1.000

      0.461

      PDX-402

      PIK3CA

      FRG1

      FRG1

      FRG1

      V344G

      L150S

      A151T

      C159Y

      0.503

      0.443

      0.445

      0.455

      PIK3CA

      GNAQ

      FRG1

      V344G

      T96S

      C159Y

      0.173

      0.098

      0.050

      PDX-409

      DNMT3A

      KEAP1

      KMT2D

      F511L

      G158C

      P1912fs

      0.653

      0.467

      0.669

      KEAP1

      KMT2D

      GNAQ

      FRG1

      DNMT3A

      G158C

      P1912fs

      T96S

      C159Y

      F511L

      0.917

      0.446

      0.063

      0.043

      0.460

      PDX-410

      TP53

      KEAP1

      KEAP1

      C124G

      G480V

      G186R

      0.564

      0.585

      0.737

      KEAP1

      KEAP1

      TP53

      G480V

      G186R

      C124G

      0.298

      0.656

      1.000

      PDX-415

      DNMT3A

      NFE2L2

      NFE2L2

      CREBBP

      TP53

      APC

      CDKN2A

      I247F

      R18Q

      D11N

      S2356F

      R337L

      ENDNG1530fs

      R52fs

      0.494

      0.584

      0.568

      0.600

      0.469

      0.559

      0.531

      AMER1

      AMER1

      APC

      CDKN2A

      CREBBP

      NFE2L2

      NFE2L2

      TP53

      DNMT3A

      FLT3

      H619R

      H619N

      -1530fs

      R52fs

      S2356F

      R18Q

      D11N

      R337L

      I247F

      M799I

      0.703

      0.698

      0.478

      0.462

      1.000

      0.364

      0.250

      1.000

      0.628

      0.076

      PDX-420

      HLA-A

      NOTCH1

      TP53

      K292E

      G427C

      H179R

      0.067

      0.575

      1.000

      PDX-434

      NOTCH2

      RRAS2

      KEAP1

      KMT2D

      TP53

      V968L

      Q72L

      Y54F

      D4400fs

      P301fs

      0.366

      0.422

      0.512

      0.509

      0.482

      IGF1R

      KEAP1

      NOTCH2

      TP53

      RRAS2

      P266S

      Y54F

      V968L

      P301fs

      Q72L

      0.204

      1.000

      1.000

      0.477

      0.792

      PDX-454

      TNFAIP3

      R52T

      0.431

      NF1

      TNFAIP3

      TP53

      LTTILKN58fs

      R52T

      P152fs

      0.476

      0.458

      0.455

      PDX-473

      CREBBP

      FLT3

      Q913R

      I920V

      0.410

      1.000

      PDX-480

      TSC2

      NF1

      NF1

      NF1

      TP53

      RRAS2

      EEF1B2

      V1695E

      N793S

      K798Q

      F1287L

      R158L

      Q143R

      R122S

      0.831

      0.169

      0.160

      0.210

      0.828

      0.034

      0.166

      NF1

      TP53

      TSC2

      W784L

      R158L

      V1695E

      0.838

      0.875

      0.516

      rsquare3.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      In PDX models of 49 patients, successful lung SCC PDX engraftment and identical histomorphology was achieved. And the 30 sets of exome sequencing analyses showed that the somatic mutations were relatively preserved. Among them, some interesting targetable mutations including BRAF(V600E) were identified. We identified consistency of transcriptome profiles of PDX models during the passages.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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