Li Chunxiang, Wang Yalong, Su Kai, Liu Yu, Wang Liyu, Zheng Bo, Yan Na, Yuan Dawei, Zhang Yanxiang, Xue Liyan, Gao Shugeng, He Jie
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Transl Lung Cancer Res. 2021 Apr;10(4):1734-1746. doi: 10.21037/tlcr-20-1001.
The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. However, information regarding the etiology of MPLC and responsiveness to epidermal growth factor receptor ()-tyrosine kinase inhibitors (TKIs) is rare. The present study aims to describe the mutation signatures of in MPLC.
Polymerase chain reaction (PCR) and Sanger sequencing were used to screen mutations in 162 family probands comprising 366 tumor lesions and 162 paired noncancerous adjacent tissues (NATs). Sequencing data from 3,243 sporadic lung adenocarcinoma (LUAD) samples were analyzed as a control.
Candidate germline mutations were observed in exons 19 (3, 1.85%), 20 (8, 4.94%) and 21 (5, 3.10%), with a total frequency of 9.88% in NATs (16/162). There were 63 probands harboring somatic mutations (63/162, 38.89%), 9 patients harbored the consistency mutations among lesions, and 8 patients carried 2 or more mutations. The overall rate of somatic mutations was lower in the MPLC probands, but those of exon 19 p.747-752del, 20 p.V769indelsVASV and 20 p.D770indelsDSVD were significantly higher in MPLC probands than in patients with sporadic LUAD.
There exists unique mutation signatures in a large cohort of MPLC probands, which might provide objective evidence of the etiology and effectiveness of clinical TKI treatment of high-risk MPLC patients.
近年来，多原发性肺癌（MPLC）患者数量迅速增加。然而，关于MPLC的病因及对表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKIs）反应性的信息却很少。本研究旨在描述MPLC中EGFR的突变特征。
采用聚合酶链反应（PCR）和桑格测序法，对162例家系先证者的366个肿瘤病灶及162个配对的癌旁非肿瘤组织（NATs）进行EGFR突变筛查。分析3243例散发性肺腺癌（LUAD）样本的测序数据作为对照。
在NATs（16/162）中，外显子19（3例，1.85%）、20（8例，4.94%）和21（5例，3.10%）观察到候选胚系突变，总频率为9.88%。有63例先证者存在体细胞突变（63/162，38.89%），9例患者的病灶间存在一致性突变，8例患者携带2个或更多突变。MPLC先证者中EGFR体细胞突变的总体发生率较低，但外显子19 p.747 - 752del、20 p.V769indelsVASV和20 p.D770indelsDSVD在MPLC先证者中的发生率显著高于散发性LUAD患者。
在一大群MPLC先证者中存在独特的EGFR突变特征，这可能为高危MPLC患者的病因及临床TKI治疗效果提供客观证据。
