Presentation of EGFR mutations in 162 family probands with multiple primary lung cancer

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 (EGFR)-tyrosine kinase inhibitors (TKIs) is rare. The present study aims to describe the mutation signatures of EGFR in MPLC.

Polymerase chain reaction (PCR) and Sanger sequencing were used to screen EGFR 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 EGFR 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 EGFR 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.