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W. Cooper
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-058 - Is Targeted next Generation Sequencing Superior to Older Methods at Identifying Actionable Mutations in Selected NSCLC Patients? (ID 2545)
09:30 - 09:30 | Author(s): W. Cooper
- Abstract
Background:
Mutation testing for clinically actionable somatic mutations is standard of care for patients with lung adenocarcinoma. Multiplex cancer panels that simultaneously assess for a range of possible mutations are available for next generation sequencing (NGS) platforms covering a wider range of genes than previously available, but it is uncertain if these provide more clinically useful information than older multiplex systems.
Methods:
We undertook targeted next generation sequencing (NGS) of paraffin embedded tumour tissue from a cohort of 13 never smokers and 18 unselected patients who underwent surgical resection of lung adenocarcinoma using the Truseq Amplicon Cancer Panel that assesses hot spots in 48 genes using the Illumina platform. Control normal tissue was obtained from non-involved lymph nodes or normal lung parenchyma obtained from the resection specimens. Results were compared to those obtained using OncoCarta™ v1.0 panel that assesses hot spots in 19 genes using mass spectrometry.
Results:
3 of the samples from the never smokers were unsuitable for NGS analysis as they failed quality control. Of the 10 samples that could be assessed, 6 (60%) had EGFR mutations (3 L858R and 3 exon 19 deletions), 1 (10%) had a KRAS G12D mutation and 5 (50%) had T53 mutations (3 in association with an EGFR mutation). Other mutations identified were ATM, PTEN and PDGFRA mutations in one of the patients that also had an EGFR mutation. All of the EGFR and KRAS mutations were also identified using the OncoCarta™ panel. Of the 3 samples that could not be assessed by NGS, 1 had an exon 19 deletion in EGFR and 1 had a BRAF V600M mutation. In the unselected patient population all of the samples passed quality control and were suitable for both NGS and mass spectrometry. Using NGS, 10/18 (55.6%) had a KRAS mutation, 3 (16.7%) had an EGFR mutation, 7 (38.9%) had a TP53 mutation, 2 (11.1%) had PIK3CA mutations and 1 (5.6%) each had a BRAF, ERBB4, MET, HRAS, STK11, HRAS, PDGFRA, CTNNB1, NOTCH1 or SMARCB1 mutation. Using the OncoCarta™ panel, all of the EGFR and KRAS mutations were identified along with only 1 of the PIK3CA mutations. The BRAF G469S mutation was not identified by mass spectrometry.
Conclusion:
NGS using a targeted cancer panel identifies more mutations than older generation multiplex mutation testing but has a higher failure rate. In the never-smoker patient group, no additional clinically actionable mutations were identified by NGS that were not found by the OncoCarta™ panel. In patient populations with a high rate of EGFR mutations, such as never smokers, there may not be much advantage to using more expensive broader NGS cancer mutation panels.
