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
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract