The Unique Genetic Mutation Characteristics Based on Large Panel Next-Generation Sequencing (NGS) Detection in Multiple Primary Lung Cancers (MPLC) Patients.

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Discovery medicine Pub Date : 2023-04-01 DOI:10.24976/Discov.Med.202335175.14

Zhu Liang, Guoxiong Zeng, Wang Wan, Biao Deng, Chunyuan Chen, Fasheng Li, Guanzhou Lin, Yuying Lin, Haitao Lin, Guixi Mo, Huilai Miao

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Abstract

Background: With the wide application of multislice spiral computed tomography (CT), the frequency of detection of multiple lung cancer is increasing. This study aimed to analyze gene mutations characteristics in multiple primary lung cancers (MPLC) using large panel next-generation sequencing (NGS) assays.

Methods: Patients with MPLC surgically removed from the Affiliated Hospital of Guangdong Medical University from Jan 2020 to Dec 2021 enrolled the study. NGS sequencing of large panels of 425 tumor-associated genes was performed.

Results: The 425 panel sequencing of 114 nodules in 36 patients showed that epidermal growth factor receptor (EGFR) accounted for the largest proportion (55.3%), followed by Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) (9.6%), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), and Kirsten rat sarcoma viral oncogene (KRAS) (8.8%). Fusion target variation was rare (only 2, 1.8%). ERBB2 Y772_A775dup accounted for 73%, KRAS G12C for about 18%, and BRAF V600E for only 10%. AT-rich interaction domain 1A (ARID1A) mutations were significantly higher in invasive adenocarcinoma (IA) which contained solid/micro-papillary malignant components (p = 0.008). The tumor mutation burden (TMB) distribution was low, with a median TMB of 1.1 MUTS/Mb. There were no differences in the TMB distribution of different driver genes. In addition, 97.2% of MPLC patients (35/36) had driver gene mutations, and 47% had co-mutations, mainly in IA (45%) and invasive adenocarcinoma (MIA) (37%) nodule, with EGFR (39.4%), KRAS (9.1%), ERBB2 (6.1%), tumor protein 53 (TP53) (6.1%) predominately.

Conclusions: MPLC has a unique genetic mutation characteristic that differs from advanced patients and usually presents with low TMB. Comprehensive NGS helps to diagnose MPLC and guides the MPLC clinical treatment. ARID1A is significantly enriched in IA nodules containing micro-papillary/solid components, suggesting that these MPLC patients may have a poor prognosis.

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基于大面板下一代测序(NGS)检测的多原发肺癌(MPLC)患者独特的基因突变特征

背景:随着多层螺旋计算机断层扫描(CT)的广泛应用，多发性肺癌的检出率越来越高。本研究旨在利用大面板下一代测序(NGS)分析多发性原发性肺癌(MPLC)的基因突变特征。方法:2020年1月至2021年12月在广东医科大学附属医院手术切除的MPLC患者纳入研究。对425个肿瘤相关基因进行了NGS测序。结果:36例114例结节的425组测序结果显示，表皮生长因子受体(EGFR)占比最大(55.3%)，其次是erbb - b2受体酪氨酸激酶2 (ERBB2)(9.6%)、v-Raf鼠肉瘤病毒致癌基因同源物B1 (BRAF)和Kirsten大鼠肉瘤病毒致癌基因(KRAS)(8.8%)。融合靶变异很少见(仅2.1.8%)。ERBB2 Y772_A775dup占73%，KRAS G12C约占18%，BRAF V600E仅占10%。富含at的相互作用域1A (ARID1A)突变在含有实体/微乳头状恶性成分的浸润性腺癌(IA)中显著升高(p = 0.008)。肿瘤突变负荷(TMB)分布较低，中位TMB为1.1 MUTS/Mb。不同驱动基因的TMB分布无差异。此外，97.2%的MPLC患者(35/36)存在驱动基因突变，47%存在共突变，主要发生在IA(45%)和浸润性腺癌(MIA)(37%)结节，以EGFR(39.4%)、KRAS(9.1%)、ERBB2(6.1%)、肿瘤蛋白53 (TP53)(6.1%)为主。结论:MPLC具有独特的基因突变特征，不同于晚期患者，通常表现为低TMB。全面的NGS有助于MPLC的诊断和指导MPLC的临床治疗。ARID1A在含有微乳头状/实性成分的IA结节中显著富集，提示这些MPLC患者可能预后较差。

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

Discovery medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Discovery Medicine publishes novel, provocative ideas and research findings that challenge conventional notions about disease mechanisms, diagnosis, treatment, or any of the life sciences subjects. It publishes cutting-edge, reliable, and authoritative information in all branches of life sciences but primarily in the following areas: Novel therapies and diagnostics (approved or experimental); innovative ideas, research technologies, and translational research that will give rise to the next generation of new drugs and therapies; breakthrough understanding of mechanism of disease, biology, and physiology; and commercialization of biomedical discoveries pertaining to the development of new drugs, therapies, medical devices, and research technology.