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Marta Salido
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P1.09 - Pathology (ID 173)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.09-32 - Concurrent Genomic Alterations in ALK-Rearranged Non-Small Cell Lung Cancer Patients (ID 2463)
09:45 - 18:00 | Author(s): Marta Salido
- Abstract
Background
Recent progress in genomic analysis using next-generation sequencing (NGS) has enabled the comprehensive detection of targetable alterations in non-small cell lung cancer (NSCLC) patients. As the detection of ALK gene fusions is being established by NGS, identification of concurrent alterations will lead to better characterization of the molecular landscape of ALK-rearranged patients.
Method
Thirty-one NSCLC samples with known ALK status (18 positive and 13 negative) tested in our Institution using FISH, IHC, and NGS (Oncomine Focus Assay, ThermoFisher Scientific) were further evaluated by an expanded NGS gene panel (PGDx elio™ tissue complete assay (under developement), Personal Genome Diagnostics). This NGS panel comprises 500+ genes and screens for clinically relevant genomic alterations (single base substitutions/insertion and deletions, fusion genes and copy number variations), and provides TMB scores (expressed as mutations per megabase, exome equivalent). Statistical associations were assessed using Pearson’s χ2 and Mann-Whitney U test.
Result
ALK positive patients were 50% female with a median age of 59 years old and 54% of them never smokers. For the ALK negative cohort, young patients without any known driver alterations were selected: 69% male with a median age of 54 years old and 92% of them current smokers. Of the 18 ALK-positive cases identified, five were considered non-evaluable for expanded genomic analysis due to insufficient sequencing coverage (yield below minimum suggested DNA input). ALK fusions were detected by all techniques in the 13 ALK-positive cases available for analysis. EML4(13)-ALK(20) was the most prevalent gene fusion detected in seven out of 13 cases (54%). Remarkably, we detected a rare ALK gene fusion that has not been yet described: IRF2BP2(1)-ALK(20). The concurrent alterations identified by expanded genomic analysis are shown in an OncoPrint figure comparing both groups. The most frequent concomitant alteration was TP53 mutation: 62% in ALK-positive and 69% ALK-negative (p> 0.05). Regarding gene amplifications, we identified three ALK-positive cases with copy number alterations of which we highlight MYC in two of these cases. Interestingly, a high TMB was significantly associated with ALK-negative cases with a median of 19.9 mut/Mb compared to 7.0 mut/Mb in ALK-positive (p= 0.001).
Conclusion
We have studied the presence of ALK fusion genes with a novel NGS panel that showed excellent correlation with standard techniques. ALK fusions can be interpreted as early strong drivers to carcinogenesis due to the low frequency of concurrent alterations. It remains to determine the clinical impact of these alterations in larger series.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-34 - Next-Generation Sequencing Implementation in Non-Small Cell Lung Cancer Molecular Diagnosis (ID 2337)
10:15 - 18:15 | Author(s): Marta Salido
- Abstract
Background
Currently, all patients with advanced non-small cell lung cancer (NSCLC) require EGFR, ALK, ROS1 and BRAF molecular characterization. Next-generation sequencing (NGS) allows the simultaneous analysis of these biomarkers optimizing both the sample and the economic cost. The purpose of this study was to compare NGS results with those obtained using single gene analysis in a prospective clinical setting.
Method
During 12 months, 50 paraffin-embedded samples from patients with advanced NSCLC (46 adenocarcinomas and four NSCLC-NOS) were prospectively analyzed in our institution. Molecular characterization was carried out using the NGS Oncomine Solid Tumor DNA and Fusion Transcript Kits for hotspot mutations and gene fusions (Thermo Fisher) and results were compared with Therascreen EGFR RGQ PCR Kit (Qiagen), and Vysis ALK and ROS1 Break Apart FISH Probe Kits (Abbott Molecular, ZytoVision).
Result
All samples studied by NGS for hotspot mutations were assessable and we detected pathogenic alterations in 90% (n= 45). Regarding targetable alterations, we identified nine patients harboring EGFR mutations (18%), in agreement with real-time PCR (except for one case which had an exon 20 insertion not interrogated by Therascreen), and one patient with a BRAF mutation (2%). We highlight the presence of TP53 mutations in 27 cases (54%), KRAS in 16 cases (32%) and STK11 in three cases (6%). TP53 mutations were concomitant with other alterations in 70% of the cases (n= 19), without being significantly associated with any of them. Gene fusion analysis by NGS was assessable in 80% of the samples (n= 40): six samples had insufficient RNA quality and four had not enough material. We detected only one case with an ALK rearrangement (2%), confirmed by FISH.
Conclusion
NGS technology for NSCLC molecular diagnosis could be considered as the initial screening test although the success rate in gene fusion assessment is closely related to RNA paraffin-embedded evaluation. NGS also detected other genomic alterations that allowed referral of patients to clinical trials.
