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- W4361951991 abstract "<div>Abstract<p><b>Purpose:</b> Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC), little is known about its molecular features. We analyzed lung LCNECs to identify biologically relevant genomic alterations.</p><p><b>Experimental Design:</b> We performed targeted capture sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC samples [65 surgically resected cases, including 10 LCNECs combined with non–small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13 advanced cases]. Frequencies of genetic alterations were compared with those of 141 SCLCs (50 surgically resected cases and biopsies of 91 advanced cases).</p><p><b>Results:</b> We found a relatively high prevalence of inactivating mutations in <i>TP53</i> (71%) and <i>RB1</i> (26%), but the mutation frequency in <i>RB1</i> was lower than that in SCLCs (40%, <i>P</i> = 0.039). In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 12 (15%) of the tumors: <i>PIK3CA</i> 3%, <i>PTEN</i> 4%, <i>AKT2</i> 4%, <i>RICTOR</i> 5%, and <i>mTOR</i> 1%. Other activating alterations were detected in <i>KRAS</i> (6%), <i>FGFR1</i> (5%), <i>KIT</i> (4%), <i>ERBB2</i> (4%), <i>HRAS</i> (1%), and <i>EGFR</i> (1%). Five of 10 cases of LCNECs combined with NSCLCs harbored previously reported driver gene alterations, all of which were shared between the two components. The median concordance rate of candidate somatic mutations between the two components was 71% (range, 60%–100%).</p><p><b>Conclusions:</b> LCNECs have a similar genomic profile to SCLC, including promising therapeutic targets, such as the PI3K/AKT/mTOR pathway and other gene alterations. Sequencing-based molecular profiling is warranted in LCNEC for targeted therapies. <i>Clin Cancer Res; 23(3); 757–65. ©2016 AACR</i>.</p></div>" @default.
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- W4361951991 date "2023-03-31" @default.
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- W4361951991 title "Data from Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung" @default.
- W4361951991 doi "https://doi.org/10.1158/1078-0432.c.6525054.v1" @default.
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