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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2018

01-06-2018 | Thoracic Oncology

Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung

Authors: Tatsuro Okamoto, MD, PhD, Kazuki Takada, MD, PhD, Seijiro Sato, MD, PhD, Gouji Toyokawa, MD, PhD, Tetsuzo Tagawa, MD, PhD, Fumihiro Shoji, MD, PhD, Ryota Nakanishi, MD, PhD, Eiji Oki, MD, PhD, Terumoto Koike, MD, PhD, Masayuki Nagahashi, MD, PhD, Hiroshi Ichikawa, MD, PhD, Yoshifumi Shimada, MD, PhD, Satoshi Watanabe, MD, PhD, Toshiaki Kikuchi, MD, PhD, Kouhei Akazawa, PhD, Stephen Lyle, MD, PhD, Kazuaki Takabe, MD, PhD, Shujiro Okuda, PhD, Kenji Sugio, MD, PhD, Toshifumi Wakai, MD, PhD, Masanori Tsuchida, MD, PhD, Yoshihiko Maehara, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2018

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Abstract

Background

Lung squamous cell carcinoma (LSCC) is a major histological subtype of lung cancer. In this study, we investigated genomic alterations in LSCC and evaluated the clinical implications of mutation burden (MB) in LSCC.

Methods

Genomic alterations were determined in Japanese patients with LSCC (N = 67) using next-generation sequencing of 415 known cancer genes. MB was defined as the number of non-synonymous mutations per 1 Mbp. Programmed death-ligand 1 (PD-L1) protein expression in cancer cells was evaluated by immunohistochemical analysis.

Results

TP53 gene mutations were the most common alteration (n = 51/67, 76.1%), followed by gene alterations in cyclin-dependent kinase inhibitor 2B (CDKN2B; 35.8%), CDKN2A (31.3%), phosphatase and tensin homolog (30.0%), and sex-determining region Y-box 2 (SOX2, 28.3%). Histological differentiation was significantly poorer in tumors with high MB (greater than or equal to the median MB) compared with that in tumors with low MB (less than the median MB; p = 0.0446). The high MB group had more tumors located in the upper or middle lobe than tumors located in the lower lobe (p = 0.0019). Moreover, cancers in the upper or middle lobes had significantly higher MB than cancers in the lower lobes (p = 0.0005), and tended to show higher PD-L1 protein expression (p = 0.0573). SOX2 and tyrosine kinase non-receptor 2 amplifications were associated with high MB (p = 0.0065 and p = 0.0010, respectively).

Conclusions

The MB level differed according to the tumor location in LSCC, suggesting that the location of cancer development may influence the genomic background of the tumor.
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Metadata
Title
Clinical and Genetic Implications of Mutation Burden in Squamous Cell Carcinoma of the Lung
Authors
Tatsuro Okamoto, MD, PhD
Kazuki Takada, MD, PhD
Seijiro Sato, MD, PhD
Gouji Toyokawa, MD, PhD
Tetsuzo Tagawa, MD, PhD
Fumihiro Shoji, MD, PhD
Ryota Nakanishi, MD, PhD
Eiji Oki, MD, PhD
Terumoto Koike, MD, PhD
Masayuki Nagahashi, MD, PhD
Hiroshi Ichikawa, MD, PhD
Yoshifumi Shimada, MD, PhD
Satoshi Watanabe, MD, PhD
Toshiaki Kikuchi, MD, PhD
Kouhei Akazawa, PhD
Stephen Lyle, MD, PhD
Kazuaki Takabe, MD, PhD
Shujiro Okuda, PhD
Kenji Sugio, MD, PhD
Toshifumi Wakai, MD, PhD
Masanori Tsuchida, MD, PhD
Yoshihiko Maehara, MD, PhD
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 6/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6401-1

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