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

Autor:	Lindquist KE; Department of Pathology, Regional Laboratories Region Skåne, Lund SE 22185, Sweden., Karlsson A; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Levéen P; Department of Pathology, Regional Laboratories Region Skåne, Lund SE 22185, Sweden., Brunnström H; Department of Pathology, Regional Laboratories Region Skåne, Lund SE 22185, Sweden.; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE 22185, Sweden., Reuterswärd C; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Holm K; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Jönsson M; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Annersten K; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Rosengren F; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden., Jirström K; Department of Pathology, Regional Laboratories Region Skåne, Lund SE 22185, Sweden.; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE 22185, Sweden., Kosieradzki J; Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund SE22185, Sweden., Ek L; Department of Respiratory Medicine and Allergology, Skane University Hospital, Lund SE22185, Sweden., Borg Å; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden.; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Medicon Village, Lund SE 22381, Sweden., Planck M; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden.; Department of Oncology, Skåne University Hospital, Lund SE 22381, Sweden., Jönsson G; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden.; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Medicon Village, Lund SE 22381, Sweden., Staaf J; Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Lund SE 22381, Sweden.; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Medicon Village, Lund SE 22381, Sweden.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 May 23; Vol. 8 (21), pp. 34796-34810.
DOI:	10.18632/oncotarget.16276
Abstrakt:	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.
Databáze:	MEDLINE
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