Liang Zhu, Zeng Guoxiong, Wan Wang, Deng Biao, Chen Chunyuan, Li Fasheng, Lin Guanzhou, Lin Yuying, Lin Haitao, Mo Guixi, Miao Huilai
The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, China.
Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University, 524000 Zhanjiang, Guangdong, China.
Discov Med. 2023 Apr;35(175):131-143. doi: 10.24976/Discov.Med.202335175.14.
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.
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.
The 425 panel sequencing of 114 nodules in 36 patients showed that epidermal growth factor receptor () accounted for the largest proportion (55.3%), followed by Erb-B2 Receptor Tyrosine Kinase 2 () (9.6%), v-Raf murine sarcoma viral oncogene homolog B1 (), and Kirsten rat sarcoma viral oncogene () (8.8%). Fusion target variation was rare (only 2, 1.8%). Y772_A775dup accounted for 73%, G12C for about 18%, and V600E for only 10%. AT-rich interaction domain 1A () mutations were significantly higher in invasive adenocarcinoma (IA) which contained solid/micro-papillary malignant components ( = 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 (39.4%), (9.1%), (6.1%), tumor protein 53 () (6.1%) predominately.
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. is significantly enriched in IA nodules containing micro-papillary/solid components, suggesting that these MPLC patients may have a poor prognosis.
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不断增加。本研究旨在使用大panel二代测序（NGS）分析多发性原发性肺癌（MPLC）的基因突变特征。
选取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大panel NGS测序。
对36例患者的114个结节进行425 panel测序，结果显示表皮生长因子受体（EGFR）占比最大（55.3%），其次是Erb-B2受体酪氨酸激酶2（HER2）（9.6%）、v-Raf鼠肉瘤病毒癌基因同源物B1（BRAF）和Kirsten大鼠肉瘤病毒癌基因（KRAS）（8.8%）。融合靶点变异少见（仅2例，1.8%）。Y772_A775dup占73%，G12C约占18%，V600E仅占10%。富含AT的相互作用结构域1A（ARID1A）突变在含有实性/微乳头恶性成分的浸润性腺癌（IA）中显著更高（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）有驱动基因突变，47%有共突变，主要在IA（45%）和浸润性非黏液腺癌（MIA）结节（37%）中，以EGFR（39.4%）、HER2（9.1%）、BRAF（6.1%）、肿瘤蛋白53（TP53）（6.1%）为主。
MPLC具有与晚期患者不同的独特基因突变特征，通常TMB较低。全面的NGS有助于MPLC的诊断并指导其临床治疗。ARID1A在含有微乳头/实性成分的IA结节中显著富集，提示这些MPLC患者预后可能较差。
