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Hong Shi
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P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.01-117 - Concurrent Gene Alterations in Treatment-Naïve EGFR-Mutant Advanced Non-Small Cell Lung Cancer (ID 13102)
16:45 - 18:00 | Author(s): Hong Shi
- Abstract
Background
EGFR-TKIs is the standard first line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). However, 20% to 30% of patients who receive EGFR-TKIs exhibit primary resistance. The gene alterations in treatment-naïve EGFR-mutant advanced NSCLC should be better explored.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed gene test results of 980 treatment-naïve advanced NSCLC samples in our institute. Tumor biopsy, ctDNA, pleural effusion or cerebrospinal fluid samples were analyzed using hybridization capture-based NGS ER-seq method, white blood cells as control, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes).
4c3880bb027f159e801041b1021e88e8 Result
Three hundreds and eighty one cases with EGFR sensitive mutation were identified, 358 adenocarcinoma, 7 squamous cell carcinoma, 1 adenosquamous carcinoma and 15 NSCLC. Among the patients, 88 patients (23.1%) harbored concurrent actionable mutations with EGFR, which 43 were exon 19 deletion, 37 were L858R and 8 were uncommon EGFR mutations. One patient had co-occurring L858R, T790M and CDKN2A frameshift mutation. The actionable mutations were from 23 genes, which involved in cellular signaling pathways, and some genes had been reported associated with EGFR-TKIs resistance (details in table). Except the actionable mutations, TP53 mutations were detected in 225 samples (59.1%, 225/381), which 35.1% (79/225) in exon8. Bcl-2–like 11(BIM) deletion were detected in 31 (8.1%, 31/381) white blood cells.
Signaling Pathways
Concurrent gene alterations
Frequency(N=88)
Cell cycle*
CDKN2A
3.9%
CDK4
2.1%
CCNE1
0.8%
CCND1
0.8%
CCND3
0.3%
PI3K/AKT/mTOR*
PIK3CA
2.9%
PTEN
1.3%
TSC1/2
1.0%
AKT2
0.3%
NF1
0.3%
RTKs*
MET
0.8%
HER2
0.8%
FGFR2
0.3%
FGFR3-TACC3
0.3%
Ras/Raf/MAPK*
KRAS
0.8%
Homologous Recombination Repair pathway
BRCA2(sc+gm)
0.8%
BRCA1(sc)
0.5%
ATM
0.5%
PALB2
0.3%
Others
CTNNB1
2.9%
MDM2
2.4%
SMARCA4
0.8%
JAK2
0.5%
sc, somatic mutation;
gm, germline mutation;
*, genes had been reported associated with EGFR-TKIs resistance
Concurrent gene alterations in treatment-naïve EGFR-mutant advanced NSCLC is common, and mutiple genes are involved. This maybe contribute to the primary resistance to EGFR-TKIs in EGFR-mutant advanced NSCLC. Indicate the importance of multiplex molecular test and further researches of target therapies.
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