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P1.02-047 Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations
November 2017 Background: RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence and clinicopathologic characteristics in RET rearrangement lung adenocarcinoma patients. The aim of this study is to investigate mRNA expressions and relationship of RET rearrangement and thymidylate synthase (TYMS) genes in NSCLC tissues. Method: The positive rate of RET rearrangement and the mRNA expressions of TYMS gene in NSCLC tissues of 642 patients were detected by using real-time fluorescent quantitative PCR method, and the relationship and its correlation between the expression and clinicopathological features were also analyzed. Result: The positive rate of RET rearrangement in NSCLC was 0.93% (6/642); High mRNA expression of TYMS gene was 63.55% (408/ 642). The expressions showed no relationship with gender, age, smoking, tumor size, lymph node metastasis and clinical stages (P>0.05). The mRNA expressions between RET rearrangement and TYMS genes showed positive correlation (P<0.05). Conclusion: Thymidylate synthase gene shows low expression level in NSCLC patients with positive RET fusion gene, which may benefit from pemetrexed of first-line chemotherapy drug. Keywords: Molecular, RET fusion gene, Thymidylate synthetase
P1.02-045 PIK3CA Mutations in Chinese Patients with Non-SmallCell Lung Cancer B. Wu,1 C. Xu,2 W. Wang,3 X. Zheng,2 W. Zhuang,1 Z. Song,3 G. Lin,1 X. Chen,4 R. Chen,5 Y. Guan,5 X. Yi,5 G. Chen,2 M. Fang,3 T. Lv,6 Y. Song6 1Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/ CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Zhejiang Cancer Hospital, Hangzhou/CN, 4Thoracic Surgery, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5Geneplus-Beijing, Beijing/CN, 6Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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 (P¼0.06). Briefly, patients with (n¼5) or without (n¼11) cooccurring EGFR mutations had a median OS of 28.5 months and 21.0 months respectively (P¼0.45); patients with (n¼4) or without (n¼12) co-occurring TP53 mutations had a median OS of 30.6 months and 21.0 months respectively (P¼0.51). 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. Keywords: Prognosis, PIK3CA, clinical features
Abstracts
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P1.02-046 Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations C. Xu,1 W. Wang,2 W. Zhuang,3 Z. Huang,3 Z. Song,2 Y. Chen,1 W. Liu,1 R. Chen,4 Y. Guan,4 X. Yi,4 G. Chen,1 M. Fang,2 T. Lv,5 Y. Song5 1Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 2 Zhejiang Cancer Hospital, Hangzhou/CN, 3Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 4Geneplus-Beijing, Beijing/CN, 5 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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%, P¼0.022), and current-smoker was much higher than no-smoker (3.17% vs 0.74%, P¼0.027), 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 complex mutations was 40.3 months. No statistically significant difference was found between the two groups (P¼0.43). Briefly, patients with (n¼8) or without (n¼7) co-occurring EGFR mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.19); patients with (n¼9) or without (n¼6) co-occurring TP53 mutations had a median OS of 40.4 months and 46.7 months respectively (P¼0.39); patients with (n¼2) or without (n¼13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.33); patients with (n¼2) or without (n¼13) cooccurring MTOR mutations had a median OS of 44.3 months and 42.6 months respectively (P¼0.71); patients with (n¼2) or without (n¼13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.33); patients with (n¼2) or without (n¼13) co-occurring APC mutations had a median OS of 39.0 months and 42.6 months respectively (P¼0.92). Conclusion: There are some significant differences 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. Keywords: Non-small-cell lung cancer, Prognosis, HER2 mutation
P1.02-047 Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations Y. Zhu,1 C. Xu,2 W. Wang,3 X. Liao,4 W. Zhuang,5 Z. Song,3 Y. Chen,2 R. Chen,6 Y. Guan,6 X. Yi,6 G. Chen,2 M. Fang,3 T. Lv,7 Y. Song7 1Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3 Zhejiang Cancer Hospital, Hangzhou/CN, 4Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing/CN, 5Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 6Geneplus-Beijing, Beijing/CN, 7 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN
S1942 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 non-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 complex mutations was 21.0 months. No statistically significant difference was found between the two groups (P¼0.06). Briefly, patients of KRAS mutations with (n¼4) or without (n¼34) co-occurring EGFR mutations had a median OS of 40.0 months and 16.3 months respectively (P¼0.07); patients with (n¼3) or without (n¼35) cooccurring TP53 mutations had a median OS of 36.4 months and 18.3 months respectively (P¼0.22); patients with (n¼3) or without (n¼35) co-occurring STK11 mutations had a median OS of not reached so far and 16.3 months respectively (P¼0.22); patients with (n¼2) or without (n¼36) co-occurring KEAP1 mutations had a median OS of 43.6 months and 16.3 months respectively (P¼0.06). Conclusion: Mutation rate of KRAS gene in current-smoker NSCLC patients was higher than nosmoker, 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. Keywords: Non-small-cell lung cancer, Prognosis, RAS
P1.02-048 Somatic Mutation Analysis of RB1 Gene in Chinese Non-Small Cell Lung Cancer Patients W. Wang,1 C. Xu,2 W. Zhuang,3 Z. Song,1 Y. Zhu,4 R. Chen,5 Y. Guan,5 X. Yi,5 M. Fang,1 T. Lv,6 Y. Song6 1Zhejiang Cancer Hospital, Hangzhou/ CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 4Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 5 Geneplus-Beijing, Beijing/CN, 6Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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
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overall survival (OS) for these patients was 32.7 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n¼3) or without (n¼4) co-occurring EGFR mutations had a median OS of 34.9 months and 30.4 months respectively (P¼0.95); patients with (n¼5) or without (n¼2) co-occurring TP53 mutations had a median OS of 32.7 months and 31.7 months respectively (P¼0.90). Conclusion: EGFR or TP53 gene accompanied may have less correlation with RB1 mutation in NSCLC patients. Chemotherapy drugs may display moderated efficacy in patients with RB1 mutation, especially, accompanied with TP53. These data have implications for both clinical trial design and therapeutic strategies. Keywords: RB1 genen mutation, Non-small-cell lung cancer, Prognosis
P1.02-049 Detection of CDKN2A Gene Mutations in Patients with Non-Small Cell Lung Cancer Patients S. Wang,1 C. Xu,2 W. Wang,3 W. Zhuang,4 Z. Song,3 Y. Zhu,5 R. Chen,6 Y. Guan,6 X. Yi,6 Y. Chen,2 G. Chen,2 M. Fang,3 T. Lv,7 Y. Song7 1 Zhejiang Cancer Hospital, Hangzhou, Zhejiang/CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Zhejiang Cancer Hospital, Hangzhou/CN, 4Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 6Geneplus-Beijing, Beijing/CN, 7 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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 (n¼4) or without (n¼4) co-occurring EGFR mutations had a median OS of 23.4 months and 33.6 months respectively (P¼0.32); patients with (n¼6) or without (n¼2) co-occurring TP53 mutations had a median OS of 23.4 months and 34.8 months respectively (P¼0.27). 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 Keywords: Non-small-cell lung cancer, Prognosis, CDKN2A mutation
P1.02-050 Pan-Can Analysis of miRNAs at the Imprinted Chromosome 14q32 Locus Reveals a Unique Pattern of Deregulation in NSCLC J. Enterina, W. Lam Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC/CA Background: Genes expressed at the imprinted chromosome 14q32 locus play crucial roles in both fetal and adult development. The protein-coding
P1.02-045 PIK3CA Mutations in Chinese Patients with Non-SmallCell Lung Cancer B. Wu,1 C. Xu,2 W. Wang,3 X. Zheng,2 W. Zhuang,1 Z. Song,3 G. Lin,1 X. Chen,4 R. Chen,5 Y. Guan,5 X. Yi,5 G. Chen,2 M. Fang,3 T. Lv,6 Y. Song6 1Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/ CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Zhejiang Cancer Hospital, Hangzhou/CN, 4Thoracic Surgery, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5Geneplus-Beijing, Beijing/CN, 6Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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 (P¼0.06). Briefly, patients with (n¼5) or without (n¼11) cooccurring EGFR mutations had a median OS of 28.5 months and 21.0 months respectively (P¼0.45); patients with (n¼4) or without (n¼12) co-occurring TP53 mutations had a median OS of 30.6 months and 21.0 months respectively (P¼0.51). 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. Keywords: Prognosis, PIK3CA, clinical features
Abstracts
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P1.02-046 Mutational Subtypes and Prognosis of Non-Small-Cell Lung Cancer Harboring HER2 Mutations C. Xu,1 W. Wang,2 W. Zhuang,3 Z. Huang,3 Z. Song,2 Y. Chen,1 W. Liu,1 R. Chen,4 Y. Guan,4 X. Yi,4 G. Chen,1 M. Fang,2 T. Lv,5 Y. Song5 1Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 2 Zhejiang Cancer Hospital, Hangzhou/CN, 3Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 4Geneplus-Beijing, Beijing/CN, 5 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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%, P¼0.022), and current-smoker was much higher than no-smoker (3.17% vs 0.74%, P¼0.027), 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 complex mutations was 40.3 months. No statistically significant difference was found between the two groups (P¼0.43). Briefly, patients with (n¼8) or without (n¼7) co-occurring EGFR mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.19); patients with (n¼9) or without (n¼6) co-occurring TP53 mutations had a median OS of 40.4 months and 46.7 months respectively (P¼0.39); patients with (n¼2) or without (n¼13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.33); patients with (n¼2) or without (n¼13) cooccurring MTOR mutations had a median OS of 44.3 months and 42.6 months respectively (P¼0.71); patients with (n¼2) or without (n¼13) co-occurring SMARCA4 mutations had a median OS of 50.6 months and 42.6 months respectively (P¼0.33); patients with (n¼2) or without (n¼13) co-occurring APC mutations had a median OS of 39.0 months and 42.6 months respectively (P¼0.92). Conclusion: There are some significant differences 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. Keywords: Non-small-cell lung cancer, Prognosis, HER2 mutation
P1.02-047 Mutational Features and Prognosis of Non-Small-Cell Lung Cancer Harboring RAS Mutations Y. Zhu,1 C. Xu,2 W. Wang,3 X. Liao,4 W. Zhuang,5 Z. Song,3 Y. Chen,2 R. Chen,6 Y. Guan,6 X. Yi,6 G. Chen,2 M. Fang,3 T. Lv,7 Y. Song7 1Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3 Zhejiang Cancer Hospital, Hangzhou/CN, 4Tumor Molecular Laboratory, Zhejiang Rongjun Hospital, Jiaxing/CN, 5Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 6Geneplus-Beijing, Beijing/CN, 7 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN
S1942 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 non-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 complex mutations was 21.0 months. No statistically significant difference was found between the two groups (P¼0.06). Briefly, patients of KRAS mutations with (n¼4) or without (n¼34) co-occurring EGFR mutations had a median OS of 40.0 months and 16.3 months respectively (P¼0.07); patients with (n¼3) or without (n¼35) cooccurring TP53 mutations had a median OS of 36.4 months and 18.3 months respectively (P¼0.22); patients with (n¼3) or without (n¼35) co-occurring STK11 mutations had a median OS of not reached so far and 16.3 months respectively (P¼0.22); patients with (n¼2) or without (n¼36) co-occurring KEAP1 mutations had a median OS of 43.6 months and 16.3 months respectively (P¼0.06). Conclusion: Mutation rate of KRAS gene in current-smoker NSCLC patients was higher than nosmoker, 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. Keywords: Non-small-cell lung cancer, Prognosis, RAS
P1.02-048 Somatic Mutation Analysis of RB1 Gene in Chinese Non-Small Cell Lung Cancer Patients W. Wang,1 C. Xu,2 W. Zhuang,3 Z. Song,1 Y. Zhu,4 R. Chen,5 Y. Guan,5 X. Yi,5 M. Fang,1 T. Lv,6 Y. Song6 1Zhejiang Cancer Hospital, Hangzhou/ CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 4Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 5 Geneplus-Beijing, Beijing/CN, 6Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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
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overall survival (OS) for these patients was 32.7 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n¼3) or without (n¼4) co-occurring EGFR mutations had a median OS of 34.9 months and 30.4 months respectively (P¼0.95); patients with (n¼5) or without (n¼2) co-occurring TP53 mutations had a median OS of 32.7 months and 31.7 months respectively (P¼0.90). Conclusion: EGFR or TP53 gene accompanied may have less correlation with RB1 mutation in NSCLC patients. Chemotherapy drugs may display moderated efficacy in patients with RB1 mutation, especially, accompanied with TP53. These data have implications for both clinical trial design and therapeutic strategies. Keywords: RB1 genen mutation, Non-small-cell lung cancer, Prognosis
P1.02-049 Detection of CDKN2A Gene Mutations in Patients with Non-Small Cell Lung Cancer Patients S. Wang,1 C. Xu,2 W. Wang,3 W. Zhuang,4 Z. Song,3 Y. Zhu,5 R. Chen,6 Y. Guan,6 X. Yi,6 Y. Chen,2 G. Chen,2 M. Fang,3 T. Lv,7 Y. Song7 1 Zhejiang Cancer Hospital, Hangzhou, Zhejiang/CN, 2Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 3Zhejiang Cancer Hospital, Hangzhou/CN, 4Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing/CN, 6Geneplus-Beijing, Beijing/CN, 7 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing/CN 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 (n¼4) or without (n¼4) co-occurring EGFR mutations had a median OS of 23.4 months and 33.6 months respectively (P¼0.32); patients with (n¼6) or without (n¼2) co-occurring TP53 mutations had a median OS of 23.4 months and 34.8 months respectively (P¼0.27). 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 Keywords: Non-small-cell lung cancer, Prognosis, CDKN2A mutation
P1.02-050 Pan-Can Analysis of miRNAs at the Imprinted Chromosome 14q32 Locus Reveals a Unique Pattern of Deregulation in NSCLC J. Enterina, W. Lam Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC/CA Background: Genes expressed at the imprinted chromosome 14q32 locus play crucial roles in both fetal and adult development. The protein-coding