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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • 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
  • Johan Staaf
Show all

Summary, in English

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.

Department/s

  • Breastcancer-genetics
  • Tumor microenvironment
  • Research Group Lung Cancer
  • Personalized Pathology & Cancer Therapy
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Create Health

Publishing year

2017-05-23

Language

English

Pages

34796-34810

Publication/Series

Oncotarget

Volume

8

Issue

21

Document type

Journal article

Publisher

Impact Journals

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Research Group Lung Cancer
  • Personalized Pathology & Cancer Therapy

ISBN/ISSN/Other

  • ISSN: 1949-2553