Brief Report: The Genomic Landscape of Small Cell Lung Cancer in Never-Smoking Patients.

IF 3.3 3区医学 Q2 ONCOLOGY

Clinical lung cancer Pub Date : 2025-03-31 DOI:10.1016/j.cllc.2025.03.011

Michael S Oh, Edward B Garon, Aaron E Lisberg, Amy L Cummings, Alex Barrett, Arya Ashok, Elizabeth Mauer, Binyam Yilma, Jonathan W Goldman

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引用次数: 0

Abstract

Background: Small cell lung cancer (SCLC) predominantly develops in patients with significant smoking history, and patients who have no history of tobacco exposure remain understudied. Prior reports have suggested that SCLC in never-smoking patients may have unique genomic traits.

Methods: We retrospectively analyzed records from the Tempus clinicogenomic database to identify SCLC patients reporting "never smoking" (NS, n = 54) or "current/former smoking" (C/FS, n = 608) status. Tumors were sequenced with the Tempus xT assay, including a targeted 648-gene DNA panel and whole exome capture RNA-seq. Tumor immune cell infiltration was estimated from RNA expression data and PD-L1 expression status was determined by immunohistochemistry.

Results: Compared with CF/S patients, NS patients were more likely to be female (70% vs. 55%). Tumors of NS patients had a lower prevalence of TP53 mutations (59% vs. 85%) but no significant difference in RB1 mutations (57% vs. 63%). NS patients had a higher prevalence of EGFR (26% vs. 2.6%), PIK3CA (15% vs. 3.6%), and OS9 (5.6% vs. 0.0%) mutations. Similar findings were observed even after removing cases of transformation from non-small cell lung cancer (NSCLC) or combined SCLCNSCLC presentations. In addition, tumors of NS patients had a lower tumor mutation burden and decreased immune cell infiltration, including by CD4+ and CD8+ T cells.

Conclusion: The mutational landscape of SCLC in NS patients significantly differs from that of C/FS patients, suggesting that the occurrence of SCLC in NS patients may represent a distinct genomic entity.

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简要报告：不吸烟患者小细胞肺癌的基因组图谱。

背景：小细胞肺癌（SCLC）主要发生在有明显吸烟史的患者中，没有烟草暴露史的患者仍未得到充分研究。先前的报道表明，不吸烟患者的SCLC可能具有独特的基因组特征。方法：我们回顾性分析来自Tempus临床基因组数据库的记录，以确定报告“从不吸烟”（NS, n = 54）或“当前/曾经吸烟”（C/FS, n = 608）状态的SCLC患者。使用Tempus xT测定法对肿瘤进行测序，包括靶向648个基因DNA面板和全外显子组捕获RNA-seq。通过RNA表达数据估计肿瘤免疫细胞浸润情况，通过免疫组织化学检测PD-L1表达状态。结果：与CF/S患者相比，NS患者以女性为主（70% vs 55%）。NS患者的肿瘤TP53突变发生率较低（59%比85%），但RB1突变发生率无显著差异（57%比63%）。NS患者的EGFR （26% vs. 2.6%）、PIK3CA （15% vs. 3.6%）和OS9 （5.6% vs. 0.0%）突变发生率较高。即使在去除非小细胞肺癌（NSCLC）或合并sccnsclc的转化病例后，也观察到类似的结果。此外，NS患者的肿瘤具有较低的肿瘤突变负担和免疫细胞浸润减少，包括CD4+和CD8+ T细胞。结论：NS患者中SCLC的突变格局与C/FS患者有显著差异，提示NS患者中SCLC的发生可能代表了一种不同的基因组实体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical lung cancer 医学-肿瘤学

CiteScore

7.00

自引率

2.80%

发文量

159

审稿时长

24 days

期刊介绍： Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.