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X. Yi
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MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
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MA 07.13 - NGS Sequencing Based Liquid / Tissue Biopsy Identified Coexistence of HER2 Amplification and Mutation in Advanced NSCLC Patients (ID 9737)
17:05 - 17:10 | Author(s): X. Yi
- Abstract
- Presentation
Background:
Human epidermal growth factor 2 (HER2, ERBB2) mutations / amplifications have been identified as oncogenic drivers in 2-5% of lung cancers. It has been reported that hybridization capture-based next-generation sequencing (NGS) could reliably detect HER2 amplification in qualified breast and gastroesophageal tumor tissue samples. However, there is little data in lung cancer, especially for advance NSCLC with only ctDNA samples available.
Method:
We reviewed 2000 consecutive samples from advanced NSCLC patients sequenced in our institute between 2015 and 2016. Tumor biopsy and/or ctDNA samples were analyzed using hybridization capture-based NGS ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations at least 59 genes (range 59 – 1021 genes).
Result:
We identified 54 samples from 48 patients with HER2-mutation or amplification in the cohort (54/2000=2.7%). The 54 samples included 14 tissue biopsy samples, 37 ctDNA samples, and 3 pleural effusion samples. Thirty-six samples carried HER2 mutations, and 23 samples carried HER2 amplification with 5 samples have concurrent HER2 mutation and amplification. A 9-base pair (bp) in-frame insertion in exon 20 (Y772_A775dup) was detected in 18 samples (18/36=50%). In addition, there were 5 other insertions in exon 20; eight single bp substitutions (S310F) in exon 8; three exon 17 V659E mutations (from the sample patient with 3 ctDNA samples submitted at different time); one exon 19 D769H mutation; and one exon 21 V842I mutation. Amplification were identified in 23 samples, with copy number range from 3.8 to 19.6 in tissue samples (n=7, medium 11.6); from 4.3 to 51.8 in ctDNA samples (n=16, medium 7.3); 3.2 and 6 in the 2 pleural effusion samples. Interestingly, the allele frequency (AF) of HER2 mutation was the maximal in 4 of the 5 patients with concurrent HER2 mutation and amplification. Two patients were EGFR-TKI resistant with EGFR L858R mutation remaining and HER2 mutation and amplification might be the major reason for the resistance.
Conclusion:
HER2 mutations might coexist with HER2 amplification in advanced NSCLC patients, and it could be detected simultaneously with hybridization capture-based NGS sequencing both in tissue and liquid biopsy samples. Further quantative analysis of HER2 amplification / mutation and anti-HER2 therapeutic effects are underway.
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OA 18 - Lung Cancer Pathology and Genetics (ID 687)
- Event: WCLC 2017
- Type: Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:George R. Simon, Yoon-La Choi
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 316
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OA 18.01 - Paired Tumor-Normal Next-Generation Sequencing (NGS) to Identify Pathogenic / Likely Pathogenic Germline Mutations in Lung Cancer Patients (ID 10326)
14:30 - 14:40 | Author(s): X. Yi
- Abstract
- Presentation
Background:
Comprehensive NGS panel based genetic testing is becoming more common to help clinicians select appropriate therapies. It has been recommended that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of genetic somatic mutations. Though it has been reported germline EGFR T790M mutations result in a unique hereditary lung cancer syndrome, little is known about germline mutation of other common hereditary cancer syndrome genes in lung cancer patients.
Method:
We reviewed the germline variants of 1000 consecutive lung cancer patients who had paired tumor-normal NGS panel sequencing in our institute between 2016 and 2017. Hybridization capture-based NGS panel sequencing enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and copy-number alterations at least 59 genes (range 59 – 1021 genes). Germline variants were interpreted following ACMG guidelines, and the variants were classified into pathogenic, likely pathogenic, variant of unknown significance, likely benign, and benign 5 classes.
Result:
Twenty-seven cases were identified to carry germline pathogenic or likely pathogenic mutations in 12 gene (2.7%): 5 with ATM ; 4 with BRCA1, BRCA2 or MSH2 respectively; 2 with CHEK2 or PMS2 respectively; 1 in ATR, CDKN2A, FANCC, MSH3, PTCH2 or RET respectively (details in table). Mean age at diagnosis was 58 (30 – 84 years) for the patients with germline mutations and 61 (29-93 years) for those without. Interestingly, none of the patients had been diagnosed with other tumors. The incidence of actionable somatic mutations of the 27 patients was similar to others: 10 patients with EGFR mutation, 3 patients with KRAS mutation, 1 patient with KIF5B-RET fusion, MET copy number gain or BRCA1 mutation respectively.No. Gene cHGVS pHGVS Mutation type 1 ATM c.1402_1403delAA p.K468Efs*18 frameshift 2 ATM c.1898+1G>C . splice 3 ATM c.2143_2144delCT p.L715Cfs*22 frameshift 4 ATM c.6019dupG p.E2007Gfs*11 frameshift 5 ATM c.903dupT p.A302Cfs*3 frameshift 6 ATR c.80_81insA p.N27Kfs*16 frameshift 7 BRCA1 c.4185+1G>A . splice 8 BRCA1 c.962G>A p.W321* nonsense 9 BRCA1 c.3340delG p.E1114Kfs*3 frameshift 10 BRCA1 c.81-2A>G . splice 11 BRCA2 c.3968_3971delAATA p.K1323Ifs*11 frameshift 12 BRCA2 c.5054C>G p.S1685* nonsense 13 BRCA2 c.6132_6135delCTTT p.F2045Hfs*5 frameshift 14 BRCA2 c.6485_6486delAA p.K2162Tfs*13 frameshift 15 CDKN2A c.73delG p.V25* frameshift 16 CHEK2 c.1010delC p.A337Efs*10 frameshift 17 CHEK2 c.1684C>T p.R562* nonsense 18 FANCC c.1257_1258insC p.T420Hfs*15 frameshift 19 MSH2 c.1165C>T p.R389* nonsense 20 MSH2 c.1A>T p.0? init-loss 21 MSH2 c.2785C>T p.R929* nonsense 22 MSH2 c.340delG p.E114Rfs*60 frameshift 23 MSH3 c.802C>T p.R268* nonsense 24 PMS2 c.1053delG p.L351Ffs*5 frameshift 25 PMS2 c.943C>T p.R315* nonsense 26 PTCH2 c.2441_2442delCT p.S814* frameshift 27 RET c.2410G>A p.V804M missense
Conclusion:
Germline mutations in common hereditary cancer syndrome genes is not rare in lung cancer patients, and it can be identified on routine matched tumor-normal NGS sequencing. Retrospective family history analysis and genetic counseling for those patients are underway.
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-002 - TP53 Mutations Predict for Poor Survival in ALK Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib (ID 8241)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Advanced non-small-cell lung cancer patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (Crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement non-small cell lung cancer (NSCLC).
Method:
66 ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. TP53 mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Result:
TP53 mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 60 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between TP53 gene wild group and mutation group patients (P=0.038, P=0.021, respectively).
Conclusion:
TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 8
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-045 - PIK3CA Mutations in Chinese Patients with Non-Small-Cell Lung Cancer (ID 8264)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability and prognosis in patients with lung adenocarcinoma. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer(NSCLC) harboring PIK3CA mutations.
Method:
A total of 517 patients with NSCLC were recruited between July 2012 and December 2014. The status of PIK3CA mutation and other genes were detected by reverse transcription polymerase chain reaction(RT-PCR) or next generation sequencing.
Result:
PIK3CA gene mutation was detected in 3.09% (16/517) NSCLC patients, including H1047R (4 patients), E545A (2 patients), E453K (2 patients), H1065Y (2 patients), E545K (1 patient), E39K (1 patient), E542K (1 patient), C420R (1 patient), K111E (1 patient) and E545K plus L781F (1 patient), and median overall survival (OS) for these patients was 23.0 months. Among them, 12 patients with co-occurring mutations had a median OS of 28.0 months, and median OS of the 4 patients without complex mutations was 21.0 months. No statistically significant difference was found between the two groups (P=0.06). Briefly, patients with (n=5) or without (n=11) co-occurring EGFR mutations had a median OS of 28.5 months and 21.0 months repectively (P=0.45); patients with (n=4) or without (n=12) co-occurring TP53 mutations had a median OS of 30.6 months and 21.0 months repectively (P=0.51).
Conclusion:
There is no significant difference of molecular features in PIK3CA gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations.
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P1.02-046 - Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations (ID 8267)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
HER2 is a driver gene identified in non-small-cell lung cancer(NSCLC). The prevalence, clinicopathology and genetic variability of HER2 mutation non-small cell lung cancer patients are unclear. The aim of this study is to investigate mutational subtypes and prognosis of NSCLC harboring HER2 mutations.
Method:
A total of 781 patients with NSCLC were recruited between July 2012 and December 2014. The status of HER2 mutation and other genes were detected by reverse transcription polymerase chain reaction (RT-PCR) or next generation sequencing.
Result:
HER2 gene mutation rate was 1.92%(15/781) in NSCLC, including S310F (2 patients), A775_G776insYVM (2 patients), S280F (2 patients), P780_Y781insGSP (1 patient), C630Y (1 patient), L755P (1 patient), T327S (1 patient), K907R (1 patient), R70W (1 patient), E117D (1 patient), L970V (1 patient), and C965S (1 patient). Mutation rate of female was much higher than male(3.76% vs 1.23%, P=0.022), and current-smoker was much higher than no-smoker(3.17% vs 0.74%, P=0.027), and median overall survival (OS) for these patients was 42.6 months. Among them, 12 patients with co-occurring mutations had a median OS of 42.6 months, and median OS of the 3 patients without cpmplex mutations was 40.3 months. No statistically significant difference was found between the two groups(P=0.43). Briefly, patients with (n=8) or without (n=7) co-occurring EGFR mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.19); patients with (n=9) or without (n=6) co-occurring TP53 mutations had a median OS of 40.4 months and 46.7 months repectively (P=0.39); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.33); patients with (n=2) or without (n=13) co-occurring MTOR mutations had a median OS of 44.3 months and 42.6 months repectively (P=0.71); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months repectively (P=0.33); patients with (n=2) or without (n=13) co-occurring APC mutations had a median OS of 39.0 months and 42.6 months repectively (P=0.92).
Conclusion:
There are some significant difference of molecular features in HER2 gene mutations with non-smoking women in NSCLC, along with the state of HER2 gene mutations little influence on prognosis. Afatinib treatment may displayed moderate efficacy in patients with HER2 mutations.
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P1.02-047 - Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations (ID 8268)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
In non-small cell lung cancer (NSCLC) RAS-mutant status is a negative prognostic and predictive factor. The prevalence, clinicopathology and genetic variability of RAS mutation NSCLC patients are unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring RAS mutations.
Method:
We retrospectively reviewed clinical features from 41 patients with RAS gene mutation NSCLC, and the survival rate was calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates.
Result:
KRAS gene mutation rate was 8.00% (38/475) in NSCLC, including G12C (9 patients), G12D (8 patients), G12V (7 patients), G12A (2 patients), G12S (2 patients), G13D (2 patients), Q61H (2 patients), G12L (1 patient), G12 (1 patient), G12K (1 patient), G12fs*3 plus G12V (1 patient), G13C plus V14I(1 patient) and K5N(1 patient). Mutation rate of current-smoker was much higher than no-smoker(15.76% and 4.41%, P<0.01), and median overall survival (OS) for these patients was 18.3 months; NRAS gene mutation rate was 0.29% (1/346), G12D, and OS for these patients was 14.2 months; HRAS gene mutation rate was 0.63% (2/315), including H27N and N85I, and median OS for both patients was 19.2 months. Among them, 18 cases of the 41 RAS mutation patients with co-occurring mutations had a median OS of 28.0 months, and median OS of the 23 patients without cpmplex mutations was 21.0 months. No statistically significant difference was found between the two groups(P=0.06). Briefly, patients of KRAS mutations with (n=4) or without (n=34) co-occurring EGFR mutations had a median OS of 40.0 months and 16.3 months repectively (P=0.07); patients with (n=3) or without (n=35) co-occurring TP53 mutations had a median OS of 36.4 months and 18.3 months repectively (P=0.22); patients with (n=3) or without (n=35) co-occurring STK11 mutations had a median OS of not reached so far and 16.3 months repectively (P=0.22); patients with (n=2) or without (n=36) co-occurring KEAP1 mutations had a median OS of 43.6 months and 16.3 months repectively (P=0.06).
Conclusion:
Mutation rate of KRAS gene in current-smoker NSCLC patients was higher than no-smoker, there is no other significant difference of molecular features in RAS gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations. Immunotherapy may displayed moderate efficacy in patients with TP53 and RAS co-exist mutations.
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P1.02-048 - Somatic Mutation Analysis of RB1 Gene in Chinese Non-Small Cell Lung Cancer Patients (ID 8310)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. The dephosphorylated RB1 protein confers the higher sensitivity to chemotherapy drug, but the RB1 mutation non-small-cell lung cancer (NSCLC) genetic variability and prognosis is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring RB1 mutations.
Method:
A total of 728 patients with NSCLC were recruited between July 2012 and December 2014. The status of RB1 mutation and other genes were detected by next generation sequencing.
Result:
RB1 gene mutation was detected in 0.96% (7/728) NSCLC patients, including p.G449E (1 patient), p.L542stop (1 patient), p.R552* (1 patient), p.Y6511fs*7 (1 patient), c.2663+2T>C (1 patient), p.P23del (1 patient) and F684fs*7 plus R418T (1 patient), and median overall survival (OS) for these patients was 32.7 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=4) co-occurring EGFR mutations had a median OS of 34.9 months and 30.4 months repectively (P=0.95); patients with (n=5) or without (n=2) co-occurring TP53 mutations had a median OS of 32.7 months and 31.7 months repectively (P=0.90).
Conclusion:
EGFR or TP53 gene accompanied may have less correlation with RB1 mutation in NSCLC patients. Chemotherapy drugs may displayed moderated efficacy in patients with RB1 mutation, especially, accompanied with TP53. These data have implications for both clinical trial design and therapeutic strategies.
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P1.02-049 - Detection of CDKN2A Gene Mutations in Patients with Non-Small Cell Lung Cancer Patients (ID 8312)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
CDKN2A is the tumor suppressor, which regulates cell cycle progression by inhibiting cyclinD-CDK4 and cyclinD-CDK6 complexes responsible for initiating the G1/S phase transition. CDKN2A gene disruption happens by different types of mutations, such as the loss of heterozygosity, homozygous deletion, or promoter silencing. There is some clinical evidence for the use of CDKN2A mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of non-small cell lung cancer(NSCLC) harboring CDKN2A mutations.
Method:
A total of 1046 patients with NSCLC were recruited between July 2012 and December 2014. The status of CDKN2A mutation and other genes were detected by next generation sequencing.
Result:
CDKN2A gene mutation was detected in 0.77% (8/1046) NSCLC patients, including p.M53I (1 patient), p.R58* (2 patients), p.R80* (2 patients), c.193+2T>C (1 patient), p.A127T (1 patient) and p.D74Y (1 patient), and median overall survival (OS) for these patients was 29.8 months. Among them, all patients were CDKN2A gene with co-occurring mutations. Briefly, patients with (n=4) or without (n=4) co-occurring EGFR mutations had a median OS of 23.4 months and 33.6 months repectively (P=0.32); patients with (n=6) or without (n=2) co-occurring TP53 mutations had a median OS of 23.4 months and 34.8 months repectively (P=0.27).
Conclusion:
EGFR and TP53 gene accompanied may have less correlation with CDKN2A mutation in NSCLC patients. CDK4/6 inhibitor palbociclib drugs may displayed moderated efficacy in patients with CDKN2A mutation.The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of NSCLC
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P1.02-056 - BRAF Non-V600E Mutations Recurrently Found in Non-Small Cell Lung Cancer in Chinese Patients (ID 8291)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Approximately half of BRAF-mutated non-small cell lung cancer (NSCLC) harbor a BRAF non-V600E mutation. Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far.
Method:
A total of 2979 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of BRAF mutation and other genes were detected by pyrophosphate sequencing or the next generation sequencing.
Result:
BRAF gene mutation rate was 0.91% (27/2979) in NSCLC, and median overall survival (OS) for these patients was 14.0 months. Among them, 17 BRAF non-V600E patients (A308T, A569T, V377D, R626K, P345T, Q530*, A320T, G652E, N581S, T167I, G466V, L597V, D594G, D594G, R389C, G469A, W531S, 62.96%) had a median OS of 11.9 months, and median OS of the 10 BRAF V600E patients (37.04%) was 24.3 months. Statistically significant difference was found between the two groups (P=0.03). Briefly, patients with (n=2)(non-V600E), (n=3)(V600E) or without (n=22) co-occurring EGFR mutations had a median OS of 25.6 months, 14.8 months and 14.8 months repectively (P=0.43); patients with (n=12)(non-V600E), (n=4)(V600E) or without (n=11) co-occurring TP53 mutations had a median OS of 11.9 months, 26.8 months and 13.9 months repectively (P=0.23); patients with (n=2)(non-V600E), (n=1)(V600E) or without (n=24) co-occurring ATM mutations had a median OS of 25.8 months, 16.0 months and 12.9 months repectively (P=0.71); patients with (n=3)(non-V600E), or without (n=24) co-occurring KRAS mutations had a median OS of 10.4 months and 15.3 months repectively (P=0.14); patients with (n=5)(non-V600E), or without (n=22) co-occurring DNMT3A mutations had a median OS of 13.4 months and 15.3 months repectively (P=0.22).
Conclusion:
This one of the largest series of patients with BRAF mutant NSCLC. Our clinical datas suggest that BRAF non-V600E mutations define specific subsets of patients with NSCLC, the value of BRAF non-V600E mutations are poor prognosis than V600E mutations. And it may benefit from combined targeted therapy with a RAF inhibitor and a MEK-inhibitor in treating BRAF non-V600E mutantion NSCLC.
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P1.02-058 - Molecular Characteristics and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NFE2L2 Mutations (ID 8293)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Recently, the nuclear factor (erythroid derived 2)-like 2 (NFE2L2) gene mutations are identified in non-small-cell lung cancer(NSCLC). While the genetic variability of NFE2L2 mutation NSCLC patients is unclear. The aim of this study is to investigate mutations and prognosis of NSCLC harboring NFE2L2 mutations.
Method:
A total of 375 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of NFE2L2 mutation and other genes were detected by the next generation sequencing.
Result:
NFE2L2 gene mutation was detected in 2.40% (9/375) in NSCLC patients, including R34Q (2 patients), R34G (2 patient), D77Y (2 patients), D29N (1 patient), E79Q (1 patient) and D29H (1 patient), stage of IIIB-IV was much higher than IA-IIIA (9.76% vs 0.34%, P<0.001), and smoker was much higher than no-smoker (4.14% vs 0.97%, P<0.001). The median overall survival (OS) for these patients was 33.6 months. Among them, 7 patients with co-occurring mutations had a median OS of 37.4 months, and median OS of the 2 patient without complex mutations was 18.1 months. No statistically significant difference was found between the two groups (P=0.12). Briefly, patients with (n=4) or without (n=5) co-occurring EGFR mutations had a median OS of 33.6 months and 28.6 months repectively (P=0.76); patients with (n=4) or without (n=5) co-occurring TP53 mutations had a median OS of 33.6 months and 19.7 months repectively (P=0.88); patients with (n=2) or without (n=7) co-occurring DNMT3A mutations had a median OS of 37.4 months and 26.7 months repectively (P=0.72).
Conclusion:
There are some significant difference of clinical features in NFE2L2 gene mutations with smoking advance non-small-cell lung cancer. TP53 accompanied mutations might play a good prognosis in NFE2L2 gene mutation non-small cell lung cancer.
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P1.02-059 - Molecular Characteristics of SMARCA4 Mutations Detection in Chinese Non-Small Cell Lung Cancer Patients (ID 8309)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
The SMARCA4 gene encodes an ATP-dependent helicase BRG1 and it belongs to SWI/SNF (switching defective/sucrose nonfermenting) complex. According to previous researches, SMARCA4 is one of the most broadly mutated subunits, developing an understanding of the mechanisms by which mutation of SMARCA4 drives cancer. The aim of this study is to investigate mutations and prognosis of NSCLC harboring SMARCA4 mutations.
Method:
A total of 1190 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of SMARCA4 mutation and other genes were detected by next generation sequencing.
Result:
SMARCA4 gene mutation was detected in 0.84% (10/1190) NSCLC patients, including R370P (1 patient), N519Kfs*15 (1 patient), Q464K (1 patient), Q1440* (2 patients), E959* (1 patient), I1400M (1 patient), E882K (1 patient), D656H (1 patient) and A379T plus A39T (1 patient), and median overall survival (OS) for these patients was 17.9 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=5) co-occurring EGFR mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.79); patients with (n=6) or without (n=4) co-occurring TP53 mutations had a median OS of 26.2 months and 16.3 months repectively (P=0.43); patients with (n=2) or without (n=8) co-occurring HER2 mutations had a median OS of 28.9 months and 14.7 months repectively (P=0.28);patients with (n=2)or without (n=9) co-occurring STK11 mutations had a median OS of 14.2 months and 26.2 months repectively (P=0.04);patients with (n=2) or without (n=8) co-occurring DNMT3A mutations had a median OS of 16.3 months and 26.2 months repectively (P=0.34); patients with (n=2) or without (n=8) co-occurring TERT mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.88).
Conclusion:
mTOR pathway may play a poor prognosis in SMARCA4 gene mutation non-small cell lung cancer. HDAC inhibitor treatment may displayed moderated efficacy in patients with SMARCA4 gene mutations. Further research on SMARCA4 gene mutation is required. Maybe a panel of biomarkers will be necessary in the future.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 4
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-004 - Gene Mutational Feature in Lung Enteric Adenocarcinoma by the Next Generation Sequencing (ID 8243)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry is close to colorectal carcinoma, but there is no associated primary colorectal carcinoma. The purpose of this study is to assess the gene mutational feature in lung enteric adenocarcinoma by the next generation sequencing.
Method:
From Feb. 2013 to Dec. 2016, 11 lung enteric adenocarcinoma patients (5 males and 6 females) received treatment from three medical centers: including Beijing, Zhejiang and Fujian. All the patients were diagnosed by pathology. Analysis was used by the next generation sequencing.
Result:
ALK/ROS1 primary point mutations were confirmed in 5 patients (71.42%, 5/7). MSH2/MSH6 point mutations were confirmed in 3 patient (42.86%, 3/7). There was no case with drive genes changed, such as EGFR mutation, ALK rearrangement, ROS1 rearrangement, RET rearrangement, MET amplification or 14 exon skipping mutation. The median overall survival (OS) of 11 lung enteric adenocarcinoma patients was 9.0 months, Subgroup analysis the median OS of ALK/ROS1 primary point mutation patients was 6.5 months, the median OS of MSH2/MSH6 primary point mutation patients was 26.0 months.
Conclusion:
ALK/ROS1 primary point mutations or MSH2/MSH6 point mutations are the most frequent feature of heterozygous mutation in our study. The MSH2/MSH6 subgroup of the median OS is longer. Further investigations will be required to validate our findings.
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P2.02-007 - Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 8289)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
STK11 is commonly mutated in non-small cell lung cancer (NSCLC). In light of recent experimental data showing that specific STK11 mutantion can acquire oncogenic activities due to the synthesis of a short STK11 isoform, The aim of this study is to investigate whether this new classification of STK11 mutants can help refine its role as a prognostic marker.
Method:
A total of 879 patients with NSCLC were recruited between July 2012 and December 2014. The status of STK11 mutation and other genes were detected by the next generation sequencing (NGS).
Result:
STK11 gene mutation rate was 0.91% (8/879) in NSCLC, including p.K269fs*18 (1 patient), p.K329stop (1 patient), c.464 plus 1G>T (1 patient), p.D194E (1 patient), p.D176V (1 patient), p.D53Tfs*11 (1 patient), p.D194A (1 patient) and p.Y118* (1 patient), and median overall survival (OS) for these patients was 22.2 months. Among them, all patients were STK11 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=6) co-occurring EGFR mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.73); patients with (n=5) or without (n=3) co-occurring TP53 mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.95); patients with (n=3) or without (n=5) co-occurring KRAS mutations had a median OS of not reached so far and 13.8 months repectively (P=0.02); patients with (n=2) or without (n=6) co-occurring SMARCA4 mutations had a median OS of 14.0 months and 37.0 months repectively (P=0.11); patients with (n=3) or without (n=5) co-occurring KEAP1 mutations had a median OS of not reached so far and 14.6 months repectively (P=0.20).
Conclusion:
STK11 mutations represent a distinct subset of NSCLC. NGS showed that STK11 mutations commonly co-existed with other driver genes. Our results show that STK11 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.
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P2.02-020 - Molecular Characteristics of Patients with PTEN Mutations in Chinese Non-Small Cell Lung Cancer (ID 8292)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a known tumor suppressor in non-small cell lung cancer (NSCLC). Because of the rarity of those mutations, associated clinical features and prognostic significance have not been thoroughly described so far. The aim of this study is to investigate mutations and prognosis of NSCLC harboring PTEN mutations.
Method:
A total of 402 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of PTEN mutation and other genes were detected by the next generation sequencing.
Result:
PTEN gene mutation was detected in 1.99% (8/402) NSCLC patients, including A333fs*10 (2 patients), D252N (1 patient), P38S (1 patient), Q171E (1 patient), S59* (1 patient), S10R(1 patient) and Y225Ifs*18(1 patient), and median overall survival (OS) for these patients was 19.7 months. Among them, 7 patients with co-occurring mutations had a median OS of 23.3 months, and OS of the 1 patient without complex mutations was 14.6 months. No statistically significant difference was found between the two groups (P=0.35). Briefly, patients with (n=5) or without (n=3) co-occurring EGFR mutations had a median OS of 33.6 months and 16.0 months repectively (P=0.33); patients with (n=4) or without (n=4) co-occurring TP53 mutations had a median OS of 14.9 months and 33.5 months repectively (P=0.18); patients with (n=2) or without (n=6) co-occurring DNMT3A mutations had a median OS of 17.8 months and 24.8 months repectively (P=0.27).
Conclusion:
Our results demonstrated that decreased PTEN gene mutation correlated with poor overall survival in non-small-cell lung cancer patients. PTEN gene mutation may define a subset of patients with lung cancer appropriate for investigational therapeutic strategies.
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P2.02-021 - Prevalence of PTPRD Gene Mutations in Chinese Non-Small Cell Lung Cancer Patients (ID 8311)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
PTPRD, encoding protein tyrosine phosphatases receptor type D, is located at chromosome 9p23-24.1, a loci frequently lost in many types of tumors. Recently, PTPRD has been proposed to function as a tumor suppressor gene. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer(NSCLC) harboring PTPRD mutations.
Method:
A total of 962 patients with NSCLC were recruited between July 2012 and December 2014. The status of PTPRD mutation and other genes were detected by next generation sequencing.
Result:
PTPRD gene mutation was detected in 0.64% (6/962) NSCLC patients, including V693F (1 patient), V330L (1 patient), T1103A (2 patients), D388Y (1 patient) and R1692G plus G1213V (1 patient), and median overall survival (OS) for these patients was 31.4 months. Among them, all patients were PTPRD gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=4) co-occurring EGFR mutations had a median OS of 41.0 months and 20.6 months repectively (P=0.06); patients with (n=4) or without (n=2) co-occurring TP53 mutations had a median OS of 27.6 months and 26.0 months repectively (P=0.79).
Conclusion:
PTPRD gene mutation coexist with other gene mutation in NSCLC. EGFR and TP53 gene accompanied may have less correlation with PTPRD mutation in NSCLC patients. Results of ongoing studies will provide more insight into effective treatment strategies for patients with PTPRD mutations.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-057 - Effectiveness of Icotinib on Uncommon EGFR Exon 20 Insert Mutations: A763_Y 764insFQEA in Non-Small-Cell Lung Cancer (ID 8286)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Clinical features of epidermal growth factor receptor (EGFR) mutations: L858R, deletions in exon 19, T790M, G719X, and L861Q in non-small-cell lung cancer (NSCLC) are well-known. The clinical significance of other uncommon EGFR mutations, such as A763_Y764insFQEA, is not well understood. This study is aimed to improve the understanding of A763_Y764insFQEA, and the clinical response to icotinib of NSCLC patients with such an uncommon mutation.
Method:
Six cases of EGFR exon 20 A763_Y764insFQEA mutation and twelve cases of EGFR exon 20 other insert mutation NSCLC patients were retrospectively analyzed until the progress of the disease or the emergence of the side effects and clinical efficacy was observed after months of followed-up.
Result:
Six cases with EGFR exon 20 A763_Y764insFQEA and twelve cases of EGFR exon 20 other insert mutation NSCLC patients mutation manifested the median PFS (9.0months vs 1.2months, P<0.001). Clinical efficacy of icotinib with advanced NSCLC harboring EGFR exon 20 mutations between A763_Y764insFQEA and other insert mutation (ORR:33.33%, DCR: 100% vs ORR: 0, DCR: 16.16%).
Conclusion:
EGFR exon 20 A763_Y764insFQEA mutation of clinical benefit from icotinib is remarkable, and it close to the common mutation of clinical benefit. It illustrates the value of in-depth molecular testing with NGS of EGFR wild type NSCLC patients.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-009 - Clinical Efficacy of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Exon 18 E709X Mutations (ID 8288)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
EGFR exon 18 E709X mutation is only reported in small case numbers of non-small cell lung cancer (NSCLC) in the literature, and their influences on the effectiveness of icotinib have not been fully understood. The study of this aim is to investigate the efficacy of icotinib in patients with NSCLC that carrying EGFR exon 18 E709X mutation.
Method:
Three cases of EGFR exon 18 E709X mutations were retrospectively analyzed until the progress of the disease or the emergence of the side effects and clinical efficacy was observed after months of followed-up.
Result:
The median progression-free survival (PFS) of three cases with EGFR exon 18 E709X (E709_T710>D, E709A, E709K plus L858R) was 3.1 months, patients with complex mutations showed a better PFS than those with single mutations (7.2 months vs. 2.7 months, P=0.225). Clinical efficacy of icotinib with advanced NSCLC harboring EGFR exon 18 E709X mutation (ORR: 66.67%, DCR: 66.67%).
Conclusion:
Icotinib is effective in patients with exon 18 E709X mutations. Patients with complex mutations benefited more from icotinib than those with single mutations.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-027 - Lung Adenocarcinoma Patient with EGFR 19 Exon Insert Mutation: I740_K745insIPVAIK and Its Response to Icotinib: A Case Report (ID 8287)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
Screening for epidermal growth factor receptor (EGFR) mutation before choosing a therapeutic strategy for patients with advanced non-small-cell lung cancer (NSCLC) is universally accepted at present. One of the reasons that certain patients without activating EGFR mutation respond to EGFR-tyrosine kinase inhibitor (TKI) treatment is possibly due to false-negative EGFR mutation. However, none of the available methods can provide the entire information of EGFR mutation; while maintaining the best sensitivity and specificity. Uncommon mutations are often evasive due to the limitation of screening methods.
Method:
A 74-year-old smoking male diagnosed with adenocarcinoma, who detected EGFR gene by reverse transcription polymerase chain reaction (RT-PCR) and the next generation sequencing (NGS)
Result:
Histopathological observations with hematoxylin and eosin staining was shown adenocarcinoma, Immunohistochemical staining for the expression of TTF-1, NapsinA and CK7. The gene detected by RT-PCR that found EGFR wild type, but it found EGFR p.I740_K745insIPVAIK and BRCA2 p.C315S by NGS. Albeit rare, this specific type of EGFR mutation deserves more attention because it was related to a good response to EGFR-TKI therapy. The patient received icotinib therapy, and icotinib therapy showed a good response. We report here, to our knowledge, the first case received icotinib in mainland China of EGFR exon 19 insert.
Conclusion:
To reduce the frequency of false negatives, hence not to lose any opportunities for a potential icotinib treatment, NGS for EGFR mutation examination according to the specimen quality and quantity (tumor load and DNA yield) is proposed.
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P3.02-080 - DNMT3A Defines a Unique Molecular Class of Chinese Non-Small Cell Lung Cancer Patients (ID 8313)
09:30 - 09:30 | Author(s): X. Yi
- Abstract
Background:
DNMT3A mutation is detected in approximately 18%-23% newly diagnosed AML patients, while the mutation is less frequently detected in cancer. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer (NSCLC) harboring DNMT3A mutations.
Method:
A total of 1367 patients with NSCLC were recruited between July 2012 and December 2014. The status of DNMT3A mutation and other genes were detected by next generation sequencing.
Result:
DMNT3A gene mutation was detected in 1.1% (15/1367) NSCLC patients, including p.V636M (1 patient), p.Y735C (1 patient), p.Y660F (1 patient), p.R183W (1 patient), p.Q653H (1 patient), p.A741P (1 patient), p.Q226* (1 patient), p.D340Y (1 patient), p.A398T (1 patient), p.A187T (1 patient), p.A910V (1 patient), p.R729W (1 patient), p.S770L (1 patient), c.1755+1G>T (1 patient) and G510D plus F545V plus R582Q (1 patient), and median overall survival (OS) for these patients was 19.7 months. Among them, all patients were DNMT3A gene with co-occurring mutations. Briefly, patients with (n=11) or without (n=4) co-occurring EGFR mutations had a median OS of 19.1 months and 22.9 months repectively (P=0.82);patients with (n=13) or without (n=2) co-occurring TP53 mutations had a median OS of 16.0 months and 29.8 months repectively (P=0.98); patients with (n=5) or without (n=10) co-occurring HER2 mutations had a median OS of 44.3 months and 14.6 months repectively (P<0.01); patients with (n=2) or without (n=13) co-occurring SMARCA4 mutations had a median OS of 32.3 months and 19.7 months repectively (P=0.43); patients with (n=2) or without (n=13) co-occurring BRCA1 mutations had a median OS of 29.6 months and 19.7 months repectively (P=0.93).
Conclusion:
EGFR, TP53, HER2, SMARCA4 and BRCA1 gene accompanied may have less correlation with DNMT3A mutation in NSCLC patients. Chemotherapy drugs may displayed moderated efficacy in patients with DMNT3A mutation. Analysis of DNMT3A mutations shows promise as a way to refine individual patients with NSCLC, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.
