P2.09-16 Heterogeneity Analyses of MSLCs—Especially in the EGFR Mutation-Positive Ones

Abstract

Multiple synchronous lung cancers (MSLCs) are diagnosed as multiple tumor nodules in the same or different lung lobes. MSLCs present a clinical dilemma whether they are primary tumors or metastases. Recent studies showed that MSLCs shared an identical germline genetic background and environmental exposure in the same individual patient, however, different tumor nodules showed highly different heterogeneity, even in all the EGFR mutation-positive focuses. Therefore, we performed this study to further analyze MSLCs as to estimate the pathology and molecule heterogeneity among these nodules. Tumor samples were obtained from nine patients diagnosed with MSLCs. Immunohistochemistry were performed by professional pathologists. Whole-exome sequencing (WES) was conducted by IlluminaNovaseq with sequencing depth of 200X. NeoTyping was used to describe the dispersion of sequencing data among MSLCs of the same patient. We found different tumor nodules showed obviously pathological and molecular heterogeneities in the same individual (Figure 1). More different dispersion was observed among the nodules with more different pathologies in the same patient. The dispersion of 20%, 50% and 100% were observed in MSLCs with the same driver genes (such as EGFR exon21 L858R and L861Q) of lung adenocarcinoma, different evolutional stages (AAH, MIA and IA) and completely different pathologies (adenocarcinoma and squamous cancer), respectively. All the sequencing data showed MSLCs had different gene information, even in all the EGFR mutation-positive nodules, maybe similar, but not the same, which supported that each nodule in one patient was independent with others. MSLCs could be independent with each other due to their pathological and molecular heterogeneities, even for EGFR mutation-positive nodules which hold the same driver gene, but different mutation site in just one patient. WES should be an effective way to recognize this heterogeneous characteristic, which would be helpful for the whole precise management of one MSLC patient.