Abstract 735: Squamous cell lung cancer with interstitial lung disease has low tumor mutation burden
Authors: Kobayashi Haruki , Serizawa Masakuni , Naito Tateaki , Konno Hayato , Kojima Hideaki , Mizuno Tetsuya , Isaka Mitsuhiro , Endo Masahiro , Nagashima Takeshi , Kusuhara Masatoshi , Urakami Kenichi , Ohshima Keiichi , Yamaguchi Ken , Ohde Yasuhisa , Takahashi Toshiaki 
Published: August 2019

Abstract
Introduction: Smoking history is considered to be related to high tumor mutation burden (TMB) in patients with non-small cell lung cancer (NSCLC). Although smoking history is also a risk factor for interstitial lung disease (ILD), characterization of TMB in NSCLC with ILD is unclear. Therefore, the present study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence numbers of TMB.
Methods: Between January 2014 and December 2015, NSCLC samples from whom underwent thoracic surgery at the Shizuoka Cancer Center were collected with informed consent and subjected to whole-exome sequencing (WES) with an Ion Proton system, and clinical factors were retrospectively reviewed using the medical records. ILD was diagnosed by high-resolution computed tomography (HRCT) or by pathological findings in resected specimens. In multivariate analyses, the parameters assessed with regard to the TMB were age, sex, histology, pathological stage, Brinkman index (BI) (400) and existence of ILD.
Results: A total of 238 samples were collected from primary tumors with a median TMB (mTMB) of approximately 2.1 mutation/Mb (M) with the range from 0.06 to 64.38. In adenocarcinoma (Ad), mTMB were approximately 1.7 M with the range from 0.06 to 64.38, and in squamous cell carcinoma (Sq), it was approximately 5.3 M with the range from 0.60 to 18.42. This study included 47 NSCLC samples with ILD. There was no significant difference in the number of TMB between tumors located outside the radiological finding of ILD and those located inside (p = 0.1085). Among 184 Ad of this study, 25 samples were with ILD. In univariate analyses, samples with male, heavy smoker and concomitant ILD showed higher TMB. Multivariate analysis showed that BI was significantly associated with the high TMB (p = 0.0009). On the other hand, among 54 Sq of this study, 22 samples were with ILD. In univariate analyses, samples with ILD showed lower TMB than those with non-ILD. Multivariate analysis showed that concomitant ILD was significantly associated with the low TMB (p = 0.0388).
Conclusions: Concomitant ILD could be associated with low TMB in Sq. Oncogenic pathway other than that activated by smoking might promote carcinogenesis of Sq with ILD. Precise molecular character of each group will be presented at the meeting.
Citation Format: Haruki Kobayashi, Masakuni Serizawa, Tateaki Naito, Hayato Konno, Hideaki Kojima, Tetsuya Mizuno, Mitsuhiro Isaka, Masahiro Endo, Takeshi Nagashima, Masatoshi Kusuhara, Kenichi Urakami, Keiichi Ohshima, Ken Yamaguchi, Yasuhisa Ohde, Toshiaki Takahashi. Squamous cell lung cancer with interstitial lung disease has low tumor mutation burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 735.