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Genomic Heterogeneity of Multiple synchronous lung cancers (MSLCs) in Chinese population


 IntroductionIt is clinically challenging to infer the phylogenetic relationship between different tumor lesions of patient with multiple synchronous lung cancers (MSLC), whether these lesions are the result of independently evolved tumor or intrapulmonary metastases.MethodsUsing Illumina X10 platform, we sequenced a total number of 128 stage I lung cancer samples collected from 64 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference.ResultsWe detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including EGFR, ERBB2, TP53, BRAF and KRAS. Other identified putative driver mutations are enriched in RTK-RAS signaling, TP53 signaling and cell cycle. Also we found some interesting cases, two cases which carried EGFR L858R and T790M co-mutation in one tumor and another tumor with only EGFR 19del, and 1 case with two KRAS hotspots in the same tumor. Due to the short follow-up time and early stage, whether the special mutation profile will affect the PFS and OS of these patients need further investigation. For the genetic evolution, among 64 tumor samples, 50 of them display distinct mutational profile, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. On the other hand, 7 patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. ConclusionIn summary, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profile in different tumor lesions and we may distinguish MSLC from intrapulmonary metastases via clonality estimation.