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Y. Zhu
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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): Y. Zhu
- 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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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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P1.01-003 - Patients Harboring a Novel PIK3CA Point Mutation after Acquired Resistance to Crizotinib in ROS1 Rearrangement Adenocarcinoma: A Case Report (ID 8245)
09:30 - 09:30 | Author(s): Y. Zhu
- Abstract
Background:
The c-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been identified in 1%-2% of non-small cell lung cancer (NSCLC) cases, these patients would benefit from the inhibitor of anaplastic lymphoma kinase (ALK), crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1 rearrangement NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1 rearrangement NSCLC is not identified completely now.
Method:
A 66-year-old female diagnosed with adenocarcinoma, who shown EGFR wild and ALK negative detected by Polymerase Chain Reaction(PCR). According to the detection of ROS1 rearrangement by the next generation sequencing (NGS) in blood after the patient received chemotherapy twice (pemetrexed and carboplatin), the addition of bevacizumab to chemotherapy 4 times (pemetrexed, carboplatin and bevacizumab) and maintenance therapy 3 times (pemetrexed and bevacizumab), crizotinib was used. Disease progressed explosively 6 months later, although the patient shown a response to crizotinib initially. Then NGS was carried out on blood again, a novel point mutation (p.L531P)of the PIK3CA gene was detected.
Result:
This case was the second report for bypass activation conferred crizotinib resistance to the patient with ROS1 rearrangement NSCLC. And it also was the first report that confirmed mTOR signaling pathways activation would lead to acquired resistance to crizotinib in the clinical. And everolimus, the mTOR signaling pathway inhibitor, was used. However, the disease of the patient was too serious, and she still died of circulatory failure. In conclusion, progression-free survival was 5.0 months and overall survival was 16.0 months.
Conclusion:
Bypass activation is one of potential resistance mechanisms to ROS1 rearrangement NSCLC conferred crizotinib and regimen for mTOR signaling pathway inhibitor may be one of the treatment options.
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 7
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-043 - A Comparison of Consistency of Detecting BRAF Gene Mutations in Peripheral Blood and Tumor Tissue of Non-Small-Cell Lung Cancer Patients (ID 8248)
09:30 - 09:30 | Author(s): Y. Zhu
- Abstract
Background:
BRAF, one of the three members of the RAF kinase family, belongs to the group of serine-threonine kinases and plays a vital role in mitogen-activated protein kinase (MAPK) pathways. Mutations of BRAF have been found in 0.5-3% of non-small-cell lung cancer (NSCLC). Among the different mutations occurring in the BRAF gene, BRAF V600E is the most common. A number of BRAF inhibitors, including sorafenib, vemurafenib and dabrafenib, are under clinical development. Thus, the detection of genetic driver mutation in lung cancer patients has become the most important tool in clinical practice. The aim is to detect the consistency of the BRAF gene mutation in peripheral blood and tumor tissue of patients with NSCLC and discuss the clinical application value of BRAF gene mutation in peripheral blood.
Method:
Real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was used to detect the tissues in 257 patients of NSCLC and the peripheral blood samples in 318 patients of NSCLC, of which 185 cases of peripheral blood specimens could match the tissue samples, and detected the BRAF gene mutation in them by comparison of mutations consistency in blood and tissue samples, and analyzed the correlation between BRAF gene mutations and clinical characteristics of patients.
Result:
The BRAF gene mutation rate was 7.23% in peripheral blood of 23 patients with NSCLC, and was 5.45% in 14 cancer tissues, the mutation consistency was 80.00% in peripheral blood tumor tissue matched samples. The consistency was statistically significant (κ=0.710, P<0.001).
Conclusion:
The consistency of the BRAF gene mutation in peripheral blood and tissue is high. BRAF gene mutations of peripheral blood could be used for clinical diagnosis and treatment in cases when tissue specimen is hard to get.
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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): Y. Zhu
- 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): Y. Zhu
- 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): Y. Zhu
- 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): Y. Zhu
- 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): Y. Zhu
- 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): Y. Zhu
- 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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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-017 - Study on the Effect of Apatinib Salvage Treatment of Advanced Non-Small Cell Lung Cancer (ID 8285)
09:00 - 09:00 | Author(s): Y. Zhu
- Abstract
Background:
No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second-or third-line treatment. The study of this aim is to investigate the effect of apatinib in advanced non-small cell lung cancer.
Method:
72 patients with advanced non-small cell lung cancer treated in our hospital from March 2014 to March 2016 were selected and given oral apatinib (750mg, qd) to tumor progression, death or toxicity intolerance so far. The objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and toxic side effects were observed and observed. Single factor analysis was used to compare the relationship between the clinical features and PFS.
Result:
The median PFS of the patients was 4.8 months (95%CI:4.7-5.0). The results of single factor analysis showed that there were no significant differences between different gender, age, PS score, histological type, drive gene mutation and metastasis foci, the number of metastasis, metastasis, treatment history, line number and duration of treatment in patients with PFS (P>0.05). The ORR of this group was 13.89%, DCR was 83.33%. According to the clinical data of 72 patients in the treatment of patients with the clinical efficacy of the waterfall plot, we can see that there are 54 cases of patients with lesions to reduce the diameter of tumor lesions as the effective treatment of the standard, there were 10 patients with of PR. There are various types of adverse events occurred in 60 patients, the incidence rate was 83.33%, including 22 cases (30.55%) for the aged III.
Conclusion:
Apatinib is a effective and safe treatment in advanced non-small cell lung cancer, and can be carried out more in-depth research and application in clinic.
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 3
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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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): Y. Zhu
- 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): Y. Zhu
- 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): Y. Zhu
- 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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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 3
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-018 - Patients Harboring ALK Rearrangement Adenocarcinoma after Acquired Resistance to Crizotinib and Transformation to SCLC: A Case Report (ID 8244)
09:30 - 09:30 | Author(s): Y. Zhu
- Abstract
Background:
Anaplastic lymphoma kinase(ALK) rearrangement responds to ALK tyrosine kinase inhibitors (TKIs) in lung cancer. Many cases ultimately acquired resistance to crizotinib. Resistance mechanisms have been described including ALK dominant or ALK non-dominant. A mechanism of transformation to small-cell lung cancer is rare.
Method:
A 54-year-old male diagnosed with adenocarcinoma, who shown EGFR wild and ALK rearrangement detected by RT-PCR and treatment with crizotinib. A re-biopsy showed a small cell lung cancer after disease progression.
Result:
The next generation sequencing (NGS) was carried out and it detected TP53 gene mutation and ALK rearrangement, no loss of retinoblastoma gene (RB). Regimen for small-cell lung cancer (SCLC) may be one of the treatment options. However, the heterogeneous tumor may be at diagnosed and the course of disease.
Conclusion:
Oncologists should realize the possibility of transformation to SCLC after patients acquire resistance to ALK-TKI therapy. A re-biopsy should be performed to enable histological and detect molecular analysis. And finding transformation to SCLC is important for choosing appropriate therapy due to the potential efficacy of standard SCLC treatments or combination of next generation AKL-TKIs.
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P3.02-067 - Lung Cancer with Concurrent EGFR Mutation and ROS1 Rearrangement: A Case Report (ID 8252)
09:30 - 09:30 | Author(s): Y. Zhu
- Abstract
Background:
ROS1 rearrangement has recently emerged as a new molecular subtype in non-small cell lung cancer (NSCLC), and is predominantly found in lung adenocarcinomas compared with other oncogenes such as EGFR, KRAS, or ALK. Patients who have both mutations are extremely rare.
Method:
A 50-year-old female diagnosed with adenocarcinoma with sarcomatoid differentiation, who was shown to have EGFR and ROS1 mutations by the next generation sequencing.
Result:
The patient was treated surgically and received three cycles of adjuvant postoperative chemotherapy. And the surgery and postoperative adjuvant chemotherapy showed a good response.
Conclusion:
For patients with this subtype, further research and experience are needed to summarize the biologic features and optimal modes of treatment, including targeted therapy in advanced lung cancer patients.
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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): Y. Zhu
- 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.
