NEOliquid: Detection of KIF5B-RET fusions in liquid biopsy samples€¦ · • detection of copy...

NEOliquid: Detection of KIF5B-RET fusions in liquid biopsy samples Roopika Menon 1 , Judith N Müller 1 , Sotirios Lakis 1 , Petra Schneider 1 , Christian Gloeckner 1 , Annina E Hube 1 , Frank Griesinger 2 , Maria Netchaeva 2 , Wilfried Eberhardt 3 , Johannes M Heuckmann 1 , Lukas C Heukamp 1 1 NEO New Oncology AG, Cologne; 2 Pius Hospital, Oldenburg; 3 Universitätsklinikum, Essen Abstract ID: #431 Proprietary NEOliquid assay: TECHNOLOGY: Chr 8 Point mutation Indel A A A A A A A A A A A Chr 10 • hybrid capture-based NGS technology • detection of point mutations, InDels and gene fusions down to an allele frequency of 0.1% • detection of copy number alterations in samples with tiny amounts of tumor DNA • provides nucleotide resolution for every genomic breakpoint • can identifiy novel fusion partners • comprehensive testing of 39 genes CASE 1: Cell-free DNA extracted from blood THE ASSAY: Hybrid capture Next Generation Sequencing (NGS) Detection of genomic alterations www.newoncology.de • 65-year old female patient • diagnosed with adenocarcinoma of the lung in 2013 • tested negative for EGFR and KRAS mutations and ALK and ROS1 translocations • treated with chemotherapy, erlotinib and radiation • progressive disease • no results from analysis of tissue due to limited material CASE 2: • 45-year old male patient • former smoker • adenocarcinoma of the lung with liver metastasis • tested negative for EGFR, KRAS, BRAF, MET, PIK3CA and TP53 mutations and ALK and ROS1 translocations • progressive disease after chemotherapy Copy number alterations Reference sequence Translocation breakpoint Loss Gain KIF5B: RESULT: • NEOliquid assay detected a KIF5B-RET translocation from a liquid biopsy (Case 1: 37 encompassing, 28 spanning reads Case 2: 1318 encompassing, 1219 spanning reads) (exemplary images of sequencing results of case 2) CONCLUSION: • Using hybrid capture-based next generation sequencing, we identified therapeutically relevant gene fusions (KIF5B-RET) in two patients previously tested negative for mutations in a selection of genes. Patients harboring this fusion may potentially benefit from treatment with tyrosine kinase inhibitors (i.e. cabozantenib or vandetanib) (REF.2). RET: REFERENCES: 1. Heuckmann and Thomas, A new generation of cancer genome diagnostics for routine clinical use: overcoming the roadblocks to personalized cancer medicine. Ann Oncol. 2015 Sep;26(9):1830-7 2. Kohno et al., KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012 Feb 12;18(3):375-7. 3. Kohno et al., Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015 Apr;4(2):156-64. (adapted and modified from REF.1) (adapted and modified from REF.3) KIF5B exon 15 (retained) RET intron 11/12 kinase domain coiled-coil kinesin motor breakpoint exon 15 exon 12 KIF5B RET coiled-coil kinesin motor 1 KIF5B 963 kinase domain RET 1 1114 transmembrane domain Cadherin fusion:

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Transcript of NEOliquid: Detection of KIF5B-RET fusions in liquid biopsy samples€¦ · • detection of copy...

Page 1: NEOliquid: Detection of KIF5B-RET fusions in liquid biopsy samples€¦ · • detection of copy number alterations in samples with tiny amounts of tumor DNA • provides nucleotide

1NEO New Oncology AG, Cologne; 2Pius Hospital, Oldenburg; 3Universitätsklinikum, Essen

Abstract ID: #431

ProprietaryNEOliquid assay:

TECHNOLOGY:

Chr 8

Pointmutation Indel

AAAA

Chr 10 • hybrid capture-based NGS technology• detection of point mutations, InDels and gene fusions down to an allele frequency of 0.1%• detection of copy number alterations in samples with tiny amounts of tumor DNA• provides nucleotide resolution for every genomic breakpoint• can identifiy novel fusion partners• comprehensive testing of 39 genes

CASE 1:

Cell-free DNA extracted from blood

THE ASSAY:

Hybrid capture Next Generation Sequencing(NGS)

Detection of genomic alterations

www.newoncology.de

• 65-year old female patient• diagnosed with adenocarcinoma of the lung in 2013• tested negative for EGFR and KRAS mutations and ALK and ROS1 translocations • treated with chemotherapy, erlotinib and radiation• progressive disease• no results from analysis of tissue due to limited material

CASE 2:

• 45-year old male patient• former smoker• adenocarcinoma of the lung with liver metastasis• tested negative for EGFR, KRAS, BRAF, MET, PIK3CA and TP53 mutations and ALK and ROS1 translocations • progressive disease after chemotherapy

Copy number alterations

Reference sequence

Translocationbreakpoint

Loss Gain

KIF5B:

RESULT:

• NEOliquid assay detected a KIF5B-RET translocation from a liquid biopsy (Case 1: 37 encompassing, 28 spanning reads Case 2: 1318 encompassing, 1219 spanning reads)

(exemplary images of sequencing results of case 2)

CONCLUSION:

• Using hybrid capture-based next generation sequencing, we identified therapeutically relevant gene fusions (KIF5B-RET) in two patients previously tested negative for mutations in a selection of genes. Patients harboring this fusion may potentially benefit from treatment with tyrosine kinase inhibitors (i.e. cabozantenib or vandetanib) (REF.2).

RET:

REFERENCES: 1. Heuckmann and Thomas, A new generation of cancer genome diagnostics for routine clinical use: overcoming the roadblocks to personalized cancer medicine.

Ann Oncol. 2015 Sep;26(9):1830-7

2. Kohno et al., KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 2012 Feb 12;18(3):375-7.

3. Kohno et al., Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015 Apr;4(2):156-64.

(adapted and modified from REF.1)

(adapted and modified from REF.3)

KIF5B exon 15 (retained) RET intron 11/12

kinase domaincoiled-coilkinesin motor

breakpoint

exon 15

exon 12

KIF5B

RET