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Poster discussion - Basic science

3398 - Homology-directed repair (HDR)-defective lung adenocarcinomas (LUACs) in circulating tumor DNA (ctDNA)


22 Oct 2018


Poster discussion - Basic science


Translational Research

Tumour Site


Niki Karachaliou


Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304


N. Karachaliou1, M. Lefterova2, J.F. Draper3, M. Molina4, I. Chaib5, R. Palmero6, A. Taus7, S. Viteri8, M. González Cao8, M. Majem Tarruella9, E. Carcereny Costa10, T. Moran10, J. Garde Noguera11, E. Felip12, S. Olsen13, M. Jackson14, M. Sampayo15, I. Faull16, D. Dix3, R. Rosell17

Author affiliations

  • 1 Institute Of Oncology Rosell, University Hospital Sagrat Cor, Grupo QuironSalud, 08029 - Barcelona/ES
  • 2 Clinical Laboratory, Guardant Health, 94063 - California/US
  • 3 Clinical Data Management, Guardant Health, 94063 - California/US
  • 4 Quirón Dexeus University Hospital, Pangaea Oncology S.L., 08028 - Barcelona/ES
  • 5 Laboratory Of Cellular And Molecular Biology, Health Sciences Research Institute of the Germans Trias i Pujol Foundation (IGTP), 08916 - Badalona/ES
  • 6 Hospital Duran I Reynals, Catalan Institute of Oncology, 08908 - Bellvitge/ES
  • 7 Medical Oncology, Hospital del Mar, 28023 - Barcelona/ES
  • 8 Medical Oncology, QuironSalud Dexeus University Institute, IOR, 8028 - Barcelona/ES
  • 9 Medical Oncology, Hospital de la Santa Creu i Sant Pau, 8026 - Barcelona/ES
  • 10 Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 8916 - Badalona/ES
  • 11 Oncology, Hospital Arnau de Vilanova, 46015 - Valencia/ES
  • 12 Medical Oncology Service (lung Cancer Unit)  , Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 13 Oncology, Guardant Health, 94063 - Redwood City/US
  • 14 Statistics, Guardant Health, 94063 - California/US
  • 15 Statistical Expert Trial Management, Medica Scientia Innovation Research – MEDSIR, 08007 - Barcelona/ES
  • 16 Business Development & Medical Affairs, Guardant Health, 08028 - Barcelona/ES
  • 17 Cancer biology & Precision Medicine Program, Germans Trias I Pujol Science Inst., Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 8916 - Badalona/ES


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Abstract 3398


Tumors lacking key HDR regulators, such as, BRCA1, BRCA2 and AT-rich interaction domain 1A (ARID1A), are hypersensitive to PARP inhibitors. Also, mutations in HDR have been associated with response to PD-1 or PD-L1 blockade. ARID1A is one of the genes with the highest mutation rate across several types of tumors. We aim to identify if HDR mutations and alterations occurred in advanced LUAC patients (p).


The Spanish Lung Liquid versus Invasive biopsy Program (SLLIP), from August 2016 to June 2017, performed genomic profiling from plasma in 185 treatment-naïve advanced LUAC p on a 73-gene ctDNA assay (Guardant360). SLLIP (NCT03248089) validated Guardant360 for the detection of LUAC targetable activating alterations. Median age 66, 64% male and 81% smokers/ex-smokers. A secondary aim was the discovery of additional drivers and actionable mutations, particularly in the absence of EGFR, KRAS, ALK and ROS alterations. Determination of deleterious mutation status was based on public databases (ClinVar and BRCA Exchange) and expert curation.


25.4% of LUAC p had any genomic alteration in DDR genes and ARID1A (BRCA1, 12; BRCA2, 13; ATM, 4; MLH1, 2; ARID1A, 24). Greater than 90% of the variants in BRCA1, BRCA2, and MLH1 were of unknown significance or likely benign. The 12 BRCA1-mutant p had a median number of 3 (range 1-15) co-occurring genetic alterations. One p had an EGFR mutation, and 4 p had KRAS mutations. The 13 BRCA2-mutant p had a median number of 4 (range 1-14) co-occurring genetic alterations. One p had EGFR, 1 p MET exon 14 and 4 p KRAS mutations. Three of 4 ATM-mutant p had co-occurring EGFR or KRAS alterations, while 3 of the ATM mutations were likely pathogenic. The 2 MLH1-mutant p had co-occurring KRAS alterations. The 24 ARID1A-mutant p had a median number of 4 (range 1-15) co-occurring genetic alterations. Six p had EGFR and 8 p KRAS mutations. More than half of the ARID1A alterations were loss-of-function mutations. The majority of SLIPP p received 1st line platinum-based chemotherapy.


For the first time ARID1A mutant p have been identified in LUAC. ctDNA could identify HDR-defective LUACs, which could aid in the use of PARP inhibitors and response to PD-1/PD-L1 blockade.

Clinical trial identification


Legal entity responsible for the study

Guardant Health Inc.


Guardant Health Inc.

Editorial Acknowledgement


All authors have declared no conflicts of interest.

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