Abstract 4468
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.
Resources from the same session
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer
Presenter: Jinsoo Lee
Session: Poster Display session 1
Resources:
Abstract
5141 - Mutational profiling of tumor tissue and sequential plasma illustrates emergent clones during treatment in late stage small cell lung cancer (SCLC)
Presenter: Stephanie Yaung
Session: Poster Display session 1
Resources:
Abstract