Genetic profiling of synchronous multiple primary lung carcinomas presenting as ground-glass opacities.

Abstract

e20034 Background: An increased incidence of synchronous multifocal pulmonary ground-glass opacities (GGOs) has been found in recent decades as a result of the advances in lung cancer screening techniques. However, little was known about the molecular mechanisms of their carcinogenesis, which may have important diagnostic, prognostic and therapeutic implications. Methods: 10 patients (pts) with clinically designated synchronous multiple primary lung cancers (sMPLC) who underwent surgical resection at our hospital were included in this study (Table). The imaging findings of all lesions were GGOs. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), enabling the simultaneous detection of mutations in 1021 cancer-associated genes. Tumor mutation burden (TMB) was calculated as the number of non-synonymous SNVs and Indels per Mb in the coding region. Results: The genetic profiles of 21 tumor lesions were analyzed. No common mutations were detected between different tumors from 70% of pts (7/10). These pts had different actionable mutations, which indicate disparate even contradictory therapeutic implications. 20% of pts (2/10) shared one driver mutation of EGFR or KRAS. Only one patient had a highly consistent mutation profiles between different GGOs. Two nodules of the patient shared 55% (6/11) of mutations, including EGFR L858R, supporting the possibility of aerogenic metastasis. The median TMB difference between nodules from one individual was 2 muts/Mb. The highest TMB difference was 16 muts/Mb, which might influence the decision of immunotherapy. Conclusions: NGS reveals independent clonality of multiple GGO lesions in most sMPLC pts, which may have contradictory therapeutic implications. In addition, it could be an auxiliary tool to differentiate intrapulmonary metastasis from multiple primary lung cancers. Therefore, broader molecular profiling is strongly advised for sMPLC pts. [Table: see text]