65P - NEOliquid: Detection of KIF5B–RET fusions in liquid biopsy samples

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Thoracic malignancies
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Lukas Heukamp
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors L. Heukamp1, R. Menon2, J. Müller2, S. Lakis2, M. Netchaeva3, F. Griesinger3, W. Eberhardt4, J.M. Heuckmann2
  • 1Department Of Diagnostics, NEO New Oncology AG, 51105 - Köln/DE
  • 2Department Of Diagnostics, NEO New Oncology AG, Köln/DE
  • 3Department Of Hematology And Oncology, Pius Hospital, Oldenburg/DE
  • 4Dept. Of Mept Of Medicine And Cancer Res., West German Tumor Center, 45122 - Essen/DE

Abstract

Background

Research in the field of molecular cancer profiling made sequencing of cell-free tumor DNA to identify targetable genomic alterations using patient blood possible. Therefore, liquid biopsy assays that can reliably detect cancer specific driver mutations in clinical routine have the potential to revolutionize cancer treatment of the future.

Methods

At NEO New Oncology AG (Cologne, Germany), we have developed a liquid biopsy assay called NEOliquid®. NEOliquid® is a hybrid-capture next-generation sequencing based assay that covers clinically relevant genomic alterations, such as point mutations, small insertions and deletions, selected gene fusions and copy number alterations within a panel of more than 30 genes. Here we describe, a 65-year-old patient who was diagnosed with an adenocarcinoma of the lung with liver metastasis, tested negative for ALK, EGFR, KRAS, and ROS1 mutations in tissue analysis. The patient was pre-treated with chemotherapy, EGFR inhibitor and radiation therapy, but still progressed after therapy before a blood sample was tested with NEOliquid®. The second patient is a 45-year-old male, diagnosed with pulmonary adenocarcinoma. Tissue analysis was negative for mutations in ALK, BRAF, EGFR, KRAS, MET, PIK3CA, ROS1, TP53 before NEOliquid® testing was performed.

Results

Following patient consent, NEOLiquid® analysis was performed on the patients' blood samples to identify oncogenic driver mutations. In both cases, a KIF5B (exon 1–15)–RET (exon 12–20) fusion was detected in the blood samples, with differences in the individual intronic breakpoints. These KIF5B-RET fusions result in the retention of the kinase domain of RET and the coiled-coil domain of KIF5B. The coiled-coil domain of KIF5B induces homodimerization, thereby activating the kinase of the KIF5B-RET fusion.

Conclusions

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. cabozantinib or vandetanib).

Clinical trial identification

-

Legal entity responsible for the study

NA

Funding

NEO New Oncology AG

Disclosure

L. Heukamp, J.M. Heuckmann: Stocks ownership and member on the advisory board. R. Menon: Virtual stock ownership. All other authors have declared no conflicts of interest.