P001 Discrepancy of Oncogenic Mutations in Bone Metastasis Derived from Lung Adenocarcinoma

Abstract

The objective of this study is to assess the different of cancer driver gene mutations in lung adenocarcinoma patients with bone metastasis using tilling PCR amplification sequencing (tPAS), a next-generation sequencing (NGS) method, and screen for the driver genes which are associated with bone metastasis of lung cancer. Fifteen clinicopathologic samples from of lung adenocarcinoma combined with bone metastasis patients were collected. Exome sequencing was conducted within 398 tumor-associated genes using CN500 NGS platform. Two hundred and twenty somatic gene mutations were detected, including point mutation, insertion, and deletion. Among all cancer driver genes, the top five gene mutations of EGFR (7/15), TP53 (7/15), ROS1 (3/15), IDH2 (2/15), and SYNE1 (2/15) were found to be mutated in lung adenocarcinoma patients; EGFR (7/15), TP53 (5/15), ADGRL3 (2/15), APC (2/15), and KMT2C (2/15) were found to be mutated in bone metastasis patients. Notably, KMT2C gene alternation was only observed in bone metastasis comparing to lung adenocarcinoma patients. In the lung adenocarcinoma mutation-negative cases, tPAS assay identified mutation frequency of EGFR (53.67%), CTNNB1 (16.01%), CASC5 (11.14%), MTOR (5.88%), FH (5.65%), and PIK3C2B (5.56%) in bone metastatic lesions. Moreover, according to over 50% mutation frequencies, the top three genes were EGFR (79.03%), ADGRL3 (75.25%), and FANCD2 (57.81%) in lung adenocarcinoma patients; the top four genes in bone metastasis patients were ADGRL3 (91.28%), EGFR (72.14%), KEAP1 (62.99%), and STK11 (55.18%). In addition, gene mutation frequencies of bone metastasis patients were higher than lung adenocarcinoma patients in EGFR (32.73%, 21.67%, 38.64%, 21.83% VS. 21.80%, 13.14%, 22.69%, 15.11%), KEAP1 (62.99% VS. 20.26%), PBRM1 (25.51% VS. 22.38), PIK3CG (44.74% VS 31.14%), TCF3 (15.00% VS. 12.38%), and TP53 (23.24% VS. 20.72), respectively. There were no significant differences (p>0.05) in correlation of tumor mutation burden (TMB) and lung cancer bone metastasis. TMB may not play a crucial role in bone metastasis. The results indicated that discrepancy of oncogenic mutations between lung adenocarcinoma and bone metastasis may be the biomarkers to predict cancer spreading. The patients with gene mutations found in bone metastases of lung adenocarcinoma suggested new potential molecular targets for diagnostics disease progression monitoring.