Background NF1 is a tumor suppressor that negatively regulates Ras signaling. NF1 mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of NF1 mutant lung cancers with comparison to tumors with KRAS mutations. Methods Between July 2013 and October 2014, 591 NSCLC tumors underwent targeted next generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. NF1 and KRAS cohorts were identified, with subsequent clinical and genomic analysis. Results Among 591 pts, 60 had NF1 mutations (10%) and 141 (24%) had KRAS mutations. 15 NF1 mutations (25%) occurred with other oncogenic mutations (BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)). There were 72 unique NF1 variants. NF1 tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, KRAS mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among NF1 tumors without concurrent oncogenic alterations, TP53 mutations/2-copy deletions occurred more often (33, 65%) than with KRAS mutation (46, 35%) (p<.001). No difference between cohorts was seen with other tumor suppressors. Conclusions NF1 mutations define a unique population of NSCLC. NF1 and KRAS mutations present in similar patient populations, but NF1 mutations occur more often with other oncogenic alterations and TP53 mutations. Therapeutic strategies targeting KRAS activation, including inhibitors of MAP kinase signaling, may warrant investigation in NF1 mutant tumors. Tumor suppressor inactivation patterns may help further define novel treatment strategies.
We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies.
Background-NF1 is a tumor suppressor that negatively regulates Ras signaling. NF1 mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of NF1 mutant lung cancers with comparison to tumors with KRAS mutations. Methods-Between July 2013 and October 2014, 591 NSCLC tumors underwent targeted next generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. NF1 and KRAS cohorts were identified, with subsequent clinical and genomic analysis. Results-Among 591 pts, 60 had NF1 mutations (10%) and 141 (24%) had KRAS mutations. 15 NF1 mutations (25%) occurred with other oncogenic mutations (BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)). There were 72 unique NF1 variants. NF1 tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, KRAS mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among NF1 tumors without concurrent oncogenic alterations, TP53 mutations/2-copy deletions occurred more often (33, 65%) than with KRAS mutation (46, 35%) (p<.001). No difference between cohorts was seen with other tumor suppressors. Conclusions-NF1 mutations define a unique population of NSCLC. NF1 and KRAS mutations present in similar patient populations, but NF1 mutations occur more often with other oncogenic
-Direct-quadrature generalized moment based methods were analysed in terms of accuracy, computational cost and robustness for the solution of the population balance problems in the [0, ) ∞ and [0,1] domains. The minimum condition number of the coefficient matrix of their linear system of equations was obtained by global optimization. An heuristic scaling rule from the literature was also evaluated. The results indicate that the methods based on Legendre generalized moments are the most robust for the finite domain problems, while the DQMoM formulation that solves for the abscissas and weights using the heuristic scaling rule is the best for the infinite domain problems.
<p>Supplemental Table 1: Identified NF1 variants; Supplemental Table 2: Tumors with multiple NF1 mutations include splice site, missense, nonsense, and frameshift mutations; Supplemental Table 3: KRAS mutations identified by next-generation sequencing.</p>
<div>Abstract<p><b>Purpose:</b><i>NF1</i> is a tumor suppressor that negatively regulates Ras signaling. <i>NF1</i> mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of <i>NF1</i> mutant lung cancers with comparison to tumors with <i>KRAS</i> mutations.</p><p><b>Experimental Design:</b> Between July 2013 and October 2014, 591 non–small cell lung cancer (NSCLC) tumors underwent targeted next-generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. <i>NF1</i> and <i>KRAS</i> cohorts were identified, with subsequent clinical and genomic analysis.</p><p><b>Results:</b> Among 591 patients, 60 had <i>NF1</i> mutations (10%) and 141 (24%) had <i>KRAS</i> mutations. 15 <i>NF1</i> mutations (25%) occurred with other oncogenic mutations [BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)]. There were 72 unique <i>NF1</i> variants. <i>NF1</i> tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, <i>KRAS</i> mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among <i>NF1</i> tumors without concurrent oncogenic alterations, <i>TP53</i> mutations/2-copy deletions occurred more often (33, 65%) than with <i>KRAS</i> mutation (46, 35%; <i>P</i> < 0.001). No difference between cohorts was seen with other tumor suppressors.</p><p><b>Conclusions:</b><i>NF1</i> mutations define a unique population of NSCLC. <i>NF1</i> and <i>KRAS</i> mutations present in similar patient populations, but <i>NF1</i> mutations occur more often with other oncogenic alterations and <i>TP53</i> mutations. Therapeutic strategies targeting <i>KRAS</i> activation, including inhibitors of MAP kinase signaling, may warrant investigation in <i>NF1</i> mutant tumors. Tumor-suppressor inactivation patterns may help further define novel treatment strategies. <i>Clin Cancer Res; 22(13); 3148–56. ©2016 AACR</i>.</p></div>
<div>Abstract<p><b>Purpose:</b><i>NF1</i> is a tumor suppressor that negatively regulates Ras signaling. <i>NF1</i> mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of <i>NF1</i> mutant lung cancers with comparison to tumors with <i>KRAS</i> mutations.</p><p><b>Experimental Design:</b> Between July 2013 and October 2014, 591 non–small cell lung cancer (NSCLC) tumors underwent targeted next-generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. <i>NF1</i> and <i>KRAS</i> cohorts were identified, with subsequent clinical and genomic analysis.</p><p><b>Results:</b> Among 591 patients, 60 had <i>NF1</i> mutations (10%) and 141 (24%) had <i>KRAS</i> mutations. 15 <i>NF1</i> mutations (25%) occurred with other oncogenic mutations [BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)]. There were 72 unique <i>NF1</i> variants. <i>NF1</i> tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, <i>KRAS</i> mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among <i>NF1</i> tumors without concurrent oncogenic alterations, <i>TP53</i> mutations/2-copy deletions occurred more often (33, 65%) than with <i>KRAS</i> mutation (46, 35%; <i>P</i> < 0.001). No difference between cohorts was seen with other tumor suppressors.</p><p><b>Conclusions:</b><i>NF1</i> mutations define a unique population of NSCLC. <i>NF1</i> and <i>KRAS</i> mutations present in similar patient populations, but <i>NF1</i> mutations occur more often with other oncogenic alterations and <i>TP53</i> mutations. Therapeutic strategies targeting <i>KRAS</i> activation, including inhibitors of MAP kinase signaling, may warrant investigation in <i>NF1</i> mutant tumors. Tumor-suppressor inactivation patterns may help further define novel treatment strategies. <i>Clin Cancer Res; 22(13); 3148–56. ©2016 AACR</i>.</p></div>
<p>Gene mutations evaluated in 275 gene panel referenced in the manuscript.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.