scholarly journals Mutation profile of non-small cell lung cancer revealed by next generation sequencing

2020 ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.

2020 ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  

Abstract Background: Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method: We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients.Results: Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.Conclusions: We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Yu-Chia Chen ◽  
Ting-Yuan Liu ◽  
Ya-Ting Lee ◽  
...  

Abstract Background Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have rarely been performed in these populations. Method We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients. Results Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions. Conclusions We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.


2007 ◽  
Vol 25 (2) ◽  
pp. 187-189 ◽  
Author(s):  
Katsunori Kagohashi ◽  
Hiroaki Satoh ◽  
Hiroichi Ishikawa ◽  
Morio Ohtsuka ◽  
Kiyohisa Sekizawa

2016 ◽  
Vol 71 (4) ◽  
Author(s):  
T. Kontakiotis ◽  
N. Manolakoglou ◽  
F. Zoglopitis ◽  
D. Iakovidis ◽  
L. Sacas ◽  
...  

Background and Aim. The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. Methods. From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. Results. Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8±9.4 vs. 62.1±8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. Conclusion. The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.


2016 ◽  
Vol 23 (1) ◽  
pp. 151-156 ◽  
Author(s):  
Judit Moldvay ◽  
Katalin Fábián ◽  
Márta Jäckel ◽  
Zsuzsanna Németh ◽  
Krisztina Bogos ◽  
...  

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4221-4221 ◽  
Author(s):  
Ashwini Bhat ◽  
Rakesh Surapaneni ◽  
Alexandre Hageboutros ◽  
Barry Milcarek ◽  
Krystal Hunter ◽  
...  

Abstract Abstract 4221 Background: There have been only limited studies on the incidence and outcome of venous thrombosis in non-small cell lung cancer patients by histology. Patients with adenocarcinoma are believed to have the highest risk of developing venous thrombosis. Objectives: 1. To study the incidence and outcome of thrombosis in patients with non- small cell lung cancer. 2. To determine the differences in the venous thrombotic risk between adenocarcinoma and squamous cell carcinoma subtypes. Patients/Methods: we conducted a retrospective chart review analysis of all the non-small cell lung cancer patients diagnosed in 2008 and 2009 at our institution. Patient and tumor characteristics as well as all venous thrombotic events (VTE) in the course of the disease were recorded. Incidence rates of VTE were calculated as both cumulative incidence and as person-time events (events per 1000 patient years of follow-up). We counted person-years of follow-up for each subject from the date of initial lung cancer diagnosis until the date of a thrombotic event, the date of death, or the end of the study period (30 June 2010), whichever occurred first. Analysis of the difference between squamous cell carcinoma and adenocarcinoma histological subgroups was done using Cox proportional Hazards model. For survival and outcome analysis of patients who develop VTE after diagnosis of lung cancer, we again used a Cox proportional Hazards model with the thrombotic event as a time -dependent variable. Results: Among133 patients with non-small cell lung cancer, 86 had adenocarcinoma, 42 had squamous cell histology and 5 were large cell carcinomas (the latter were excluded from the analysis). The mean age of the patients was 66.2 years and their median survival was 377 days (1.04 years).We observed 25 events of VTE over 82.89 years of follow-up for an overall incidence of VTE of 301.6 per 1000 person-years. Among 86 patients with adenocarcinoma histology, we found 21 VTEs (24.4%) Among 42 patients with squamous cell carcinoma, 4 VTE s occurred (9.5 %). The incidence of VTE for patients with adenocarcinoma was 422 per 1000 person-years (95% CI: 282 – 568) and for patients with squamous cell carcinoma 125.97 per 1000 person-years (95 % CI: 36 – 298) resulting in a trend towards higher VTE incidence in patients with adenocarcinoma as compared to patients with squamous cell carcinoma. When the rate ratio between the adenocarcinoma (21/49.7) and squamous cell cancer (4/31.8) are compared, the rate ratio is 3.359 (1.207 – 9.352). The risk of developing a VTE was 2 fold increased for patients with adenocarcinoma vs. squamous cell carcinoma (crude hazard ratio 2.375 [95%CI: 0.664–8.491]) There was a trend towards lower survival time in patients who develop a VTE during the course of their disease compared to patients who did not develop a VTE. (HR 0.992, 95% CI:.449 – 2.193). 5 of the 21 patients in the adenocarcinoma group who had VTE had a second VTE despite anticoagulation. Discussion: Only few studies have described the absolute risk as incidence rates of VTE in lung cancer patients. One study in 2004 reported the incidence of VTE is 20-fold increased in lung cancer patients compared to general population; with 3-fold increase in patients with adenocarcinoma histology. Our study confirms the trend towards increased risk of VTE in adenocarcinoma histology, along with a worse outcome. Also, of interest, is the unusually high incidence of VTE noted in our study cohort compared to the reference studies (20.9% vs. 7.2%). This finding might be due to the enhanced awareness and high clinical suspicion leading to increased testing for VTE in the cancer patients. Based on these findings, prophylactic anticoagulation in these patients may be warranted to prevent development of venous thrombosis. This needs to be studied in a prospective clinical trial in the future. Disclosures: No relevant conflicts of interest to declare.


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