Anaplastic lymphoma kinase (ALK) partners identified by next-generation sequencing in Chinese patients with solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3555-3555
Author(s):  
Sheng Yang ◽  
Fuyu Gong ◽  
Guoqiang Wang ◽  
Xiaohui He
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Chinese Patients ◽  
Fusion Partner ◽  
The Novel ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Anaplastic Lymphoma ◽  
Generation Sequencing

3555 Background: Anaplastic lymphoma kinase (ALK) rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC). More than 30 different fusion partner genes of ALK in NSCLC have been reportedand most of these ALK fusions respond well to ALK inhibitors crizotinib. With the development of next-generation sequencing (NGS), more novel partners for ALK rearrangement have been identified. Here, we aimed to report the landscape of ALK rearrangement in Chinese patients with solid tumors. Methods: Tissue or blood samples were subjected to NGS in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for ALK arrangement. Results: In total, we profiled more than 40,000 patients, among which 72 cases with 52 ALK fusion partner, harboring 17 reported partners and 35 novel partners. The average ALK rearrangement patients' age was 53 years (range, 17-76 years). Among all the ALK fusion cases (n = 72), lung cancer were the largest proportion with 77.8% (n = 56), colorectal cancer accounted for, 5.5% (n = 4), liver cancer accounted for 4.2% (n = 3), biliary cancer, melanoma, carcinosarcoma and inflammatory myofibroblastic tumor accounted for 2.8% (n = 2) respectively, and only one case (n = 1) was malignant peritoneal mesothelioma. The most common ALK fusion partners were KIF5B (n = 6), DCTN1 (n = 5) and STRN (n = 5). In 38 cases, 35 novel ALK fusion partners were discovered. The novel CLIP4-ALK, EHBP1-ALK, PLB1-ALK occurred twice in 6 patients, which were two lung cancer patients with CLIP4-ALK fusion, two lung cancer patients with PLB1-ALK fusion, one hepatic cellular cancer patients with EHBP1-ALK, and one melanoma patients with EHBP1-ALK. There were two special lung cancer cases with two ALK fusions. One case detected the novel LRIG1-ALK fusion and novel PLB1-ALK fusion, the other case detected novel GLI3-ALK fusion and reported HIP1-ALK fusion. Conclusions: Novel ALK fusions are detected in patients with not only NSCLC but also other solid tumors. NGS fusion assay is an optional method for screening novel fusions.

scholarly journals Molecular characteristics and clinical outcomes of complex ALK rearrangements identified by next-generation sequencing in non-small cell lung cancers

2021 ◽  
Author(s):  
Peiyi Xia ◽  
Lan Zhang ◽  
Pan Li ◽  
Enjie Liu ◽  
Wencai Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Small Cell ◽  
Molecular Characteristics ◽  
Fusion Partner ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Generation Sequencing

Abstract Background Complex kinase rearrangement, a mutational process involving one or two chromosomes with clustered rearrangement breakpoints, interferes with the accurate detection of kinase fusions by DNA-based next-generation sequencing (NGS). We investigated the characteristics of complex ALK rearrangements in non-small cell lung cancers using multiple molecular tests. Methods Samples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results In a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n = 3), intragenic (n = 5) and “bridge joint” rearrangements (n = 6). All thirteen cases with sufficient samples actually expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex ALK rearrangements who received ALK inhibitors treatment (n = 6), showed no difference in progression-free survival (PFS) compared with patients with canonical ALK fusions(n = 36, P = 0.9291). Conclusions This study firstly reveals the molecular characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex ALK rearrangements in clinical practice for optimal treatment decision.

scholarly journals Molecular characteristics and clinical outcomes of complex ALK rearrangements identified by next-generation sequencing in non-small cell lung cancers

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peiyi Xia ◽  
Lan Zhang ◽  
Pan Li ◽  
Enjie Liu ◽  
Wencai Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Small Cell ◽  
Molecular Characteristics ◽  
Fusion Partner ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Generation Sequencing

Abstract Background Complex kinase rearrangement, a mutational process involving one or two chromosomes with clustered rearrangement breakpoints, interferes with the accurate detection of kinase fusions by DNA-based next-generation sequencing (NGS). We investigated the characteristics of complex ALK rearrangements in non-small cell lung cancers using multiple molecular tests. Methods Samples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results In a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring ALK rearrangements were identified. Fourteen cases with complex ALK rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n = 3), intragenic (n = 5) and “bridge joint” rearrangements (n = 6). All thirteen cases with sufficient samples actually expressed canonical EML4-ALK fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex ALK rearrangements who received ALK inhibitors treatment (n = 6), showed no difference in progression-free survival (PFS) compared with patients with canonical ALK fusions n = 36, P = 0.9291). Conclusions This study firstly reveals the molecular characteristics and clinical outcomes of complex ALK rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex ALK rearrangements in clinical practice for optimal treatment decision.

scholarly journals Demographics, Risk Factors and Survival Analysis of Lung Cancer in Young Adults (<30 Years) in China-A Retrospective Cohort Study

2021 ◽  
Author(s):  
Jingjing Qu ◽  
Minjia Qian ◽  
Farhin Shaheed Kalyani ◽  
Wenzeng Xu ◽  
Qian Shen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Young Adults ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Stage Iv ◽  
Age Group ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Anaplastic Lymphoma

Abstract Background Lung cancer in very young adults in China aged <30 is on the rise and the clinicopathological characteristics of this unique population are incomplete and are yet to be elucidated. Our study aims to explore the characteristics, trends and distinctive features of lung cancer this age group to provide more information that can aid in developing optimal treatment regimens and improve prognosis for this exclusive age group. Method A retrospective review of 141 lung cancer patients admitted at our hospital from August 2011 to October 2021 was performed. The focused age group in our study was 18-30 years old. The data collected included demographics, tumor pathology, gene mutations, and treatment. Overall survival and prognosis were systematically analyzed. Results From a total of 141 of young lung cancer patients, 139 were included in final analysis. The gender distribution in our series favored female(65.5%), and only 7.2% of the study cohort had a history of smoking. Adenocarcinoma was the most common histological type in our study, presenting 93.5% of all patients. The most common stages at diagnosis was stage I(61.2%) and stage IV(30.2%). Genetic testing was performed in only 24.5% (34/139) of the patients. From the 23/34 patients in our study who tested positive for a genetic mutation, 19 (82.3%) were stage IV. The most common gene mutation was Anaplastic Lymphoma kinase(ALK) rearrangement observed in 13/23 (56.5%) gene mutation positive patients. Among stage IV NSCLC, OS was longer in patients who received targeted therapy, compared to the patients not receiving target therapy: 88 months vs 24 months (95% CI: 0.15-1.0, p=0.0282). Conclusion Lung cancer in the young adult population has particular characteristics (Common in female, non-smoker and adenocarcinoma patients). Higher stages of disease were observed in those with a gene mutation (notably ALK rearrangement). Although the sample size was small, the current data suggests a higher mutation rate in the younger population. These findings have fundamental implications for practice and we propose that all patients under 30 diagnosed with lung cancer should undergo genetic testing so they can receive personalized treatment and therefore achieve better outcomes.

Spectrum of Pathogenic Germline Mutations in Chinese Lung Cancer Patients through Next-Generation Sequencing

2019 ◽  
Vol 26 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Panwen Tian ◽  
Xiangyang Cheng ◽  
Zhengyi Zhao ◽  
Yuzi Zhang ◽  
Celimuge Bao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Cancer Patients ◽  
Germline Mutations ◽  
Next Generation ◽  
Lung Cancer Patients ◽  
Generation Sequencing
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