552P - Genome characteristics of stage I lung adenocarcinoma associated with distinct progression patterns

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Non-small-cell lung cancer
Translational Research
Presenter Ee Ke
Citation Annals of Oncology (2016) 27 (suppl_9): ix179-ix180. 10.1093/annonc/mdw601
Authors E. Ke, F. Niu, N. Zhao, W. Deng, W. Zhong, Q. Zhou, Y. Wu
  • Guangdong Lung Cancer Institute, Guangdong General Hospital, 510080 - Guangzhou/CN

Abstract

Background

The low-dose CT screening results in a reduction in mortality from lung cancer. However, the limitation of screening is overdiagnosis and overtreatment. Once we can predict the behavior of the cancer, i.e., whether it is indolent or actually threatens the patient’s life, we will be able to give better advice.

Methods

The study included 17 cases with stage I lung adenocarcinoma. The indolent group contained 10 patients whose tumor grew very slowly in nearly 2-year-follow-up and the aggressive group contained 7 patients whose disease-free-survival (DFS) was less than 6 months and overall survival (OS) less than 2 years. DNA was extracted from the tumor and their matched normal lung tissue from the patients enrolled in our study. The paired-end multiplex exome sequencing of DNA was performed on the Illumina HiSeq 2500 sequencing platform.

Results

The mean depth of the sequence was 90x. The mean number of exonic mutations per sample was 132 (range 42 to 287) in aggressive group versus 54 (range 26 to 95) in indolent lung cancers (P = 0.035). A numerically higher frequency of C>A nucleotide transversion was identified in aggressive lung cancers whereas the C>T transition was the most frequent substitutions in indolent group. Mut-driver genes included EGFR (6), APC (1), PIK3R1 (1), GNAS (1), CRLF2 (1) in tumors displaying an indolent behavior, and KRAS (4), EGFR (2), TP53 (3), ALK (1), PIK3CA (1), MAP2K1 (1), PDGFRA (1), CARD11 (1) in aggressive arm. Pathway analysis using KEGG database showed that more pathways were activated in aggressive group, but none in the indolent group. Based on the GO terms and KEGG annotation, these unigenes of aggressive cancers were highly suggested to be involved in cell adhesion.

Conclusions

The work suggested that genomic instability contributes to the poor prognosis of stage I lung adenocarcinoma. The prognosis is associated with the mutation burden and mutational spectrum. The activation of the genes in cell adhesion pathways may predict the recurrence and metastasis of lung cancer.

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.