4468 - Genomic Heterogeneity and Clonality Analysis of Multiple synchronous lung cancers (MSLCs)

Background

It 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.

Methods

Using Illumina X ten platform, we sequenced a total number of 49 lung adenocarcinoma samples collected from 24 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference. Clonality estimation was further carried out to determine the mutational similarity of different tumor lesions.

Results

Among 24 patients, 17 of them display distinct mutational profile, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. The phylogenetic analysis suggests that multiple cancerous lesions in these patients most likely evolve from different progenitor cells. On the other hand, seven patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. The mutation spectra of single-nucleotide variations (SNVs) were fairly consistent across different cancerous lesion within all patients. We detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including KRAS, MET, EGFR, TP53, and BRAF. Other identified putative driver mutations are enriched in RTK-RAS signaling, TP53 signaling and cell cycle.

Conclusions

Our findings show that, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profile in different tumor lesions and we are able to distinguished MSLC from intrapulmonary metastases via clonality estimation. This study delineates the evolutionary trajectories of MSLCS and shed light on better therapeutic strategy and prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The First Affiliated Hospital of Dalian Medical University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.