Oncotarget

Research Papers:

Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer

Kajsa Ericson Lindquist _, Anna Karlsson, Per Levéen, Hans Brunnström, Christel Reuterswärd, Karolina Holm, Mats Jönsson, Karin Annersten, Frida Rosengren, Karin Jirström, Jaroslaw Kosieradzki, Lars Ek, Åke Borg, Maria Planck, Göran Jönsson and Johan Staaf

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Oncotarget. 2017; 8:34796-34810. https://doi.org/10.18632/oncotarget.16276

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Abstract

Kajsa Ericson Lindquist1,*, Anna Karlsson2,*, Per Levéen1, Hans Brunnström1,3, Christel Reuterswärd2, Karolina Holm2, Mats Jönsson2, Karin Annersten2, Frida Rosengren2, Karin Jirström1,3, Jaroslaw Kosieradzki4, Lars Ek4, Åke Borg2,5, Maria Planck2,6, Göran Jönsson2,5 and Johan Staaf2,5

1Department of Pathology, Regional Laboratories Region Skåne, Lund SE 22185, Sweden

2Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden

3Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE 22185, Sweden

4Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund SE22185, Sweden

5CREATE Health Strategic Center for Translational Cancer Research, Lund University, Medicon Village, Lund SE 22381, Sweden

6Department of Oncology, Skåne University Hospital, Lund SE 22381, Sweden

*These authors have contributed equally to this work

Correspondence to:

Johan Staaf, email: johan.staaf@med.lu.se

Keywords: lung cancer, NGS, gene fusion, mutation, precision medicine

Received: November 01, 2016     Accepted: March 01, 2017     Published: March 16, 2017

ABSTRACT

Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics.


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