Papers

International journal
Feb, 2021

Mutational signatures in squamous cell carcinoma of the lung.

Journal of thoracic disease
  • Atsushi Osoegawa
  • Kazuki Takada
  • Tatsuro Okamoto
  • Seijiro Sato
  • Masayuki Nagahashi
  • Tetsuzo Tagawa
  • Masanori Tsuchida
  • Eiji Oki
  • Shujiro Okuda
  • Toshifumi Wakai
  • Masaki Mori
  • Display all

Volume
13
Number
2
First page
1075
Last page
1082
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.21037/jtd-20-2602

Background: Tumor mutational burden (TMB) has been identified as one of the predictors for the response to anti-programmed cell death-1 (anti-PD-1) antibody therapy and reported to correlate with smoking history in lung adenocarcinoma. However, in squamous cell carcinoma of the lung, the association between TMB and clinicopathological background factors, such as smoking history, has not been reported, including in our previous study. The mutational signature is a tool to identify the mutagens that are contributing to the mutational spectrum of a tumor by investigating the pattern of DNA changes. Here, we analyzed the mutational signature in lung squamous cell carcinoma to identify mutagens affecting the TMB. Methods: Seven representative mutational signatures including signature 7 (SI7) [ultraviolet (UV)-related], SI4 (smoking), SI6/15 [mismatch repair (MMR)], SI2/13 [apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)], and SI5 (clock-like) were analyzed in Japanese patients with lung squamous cell carcinoma (n=67) using data generated by next-generation sequencing consisting of a 415-gene panel. The relationships between signatures and clinico-pathological data including TMB and programmed death-ligand 1 (PD-L1) expression were analyzed. Results: Although the reconstructed mutational counts were small with targeted sequencing (median: 30.1, range: 13.3-98.7), the distributions of signatures were comparable among samples, with 56 cases containing more than four signatures. The smoking-related SI4 was found in 45 cases and was significantly related with pack-year index (PYI) (P=0.026). The reconstructed mutation counts were highly correlated with SI4 (r=0.51, P<0.0001), whereas the correlation was weak with SI6/15 (MMR-related) and SI2/13 (APOBEC-related). There was no mutational signature related with PD-L1 expression. Some patients exhibited unique signatures; the patient with the highest mutational counts had a MMR signature, and another patient with a prominent UV signature had occupational exposure to UV, as he was employed as a neon sign engineer. Conclusions: Mutational signatures can predict the cause of lung squamous cell carcinoma. Tobacco smoking is the mutagen most related with TMB.

Link information
DOI
https://doi.org/10.21037/jtd-20-2602
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33717580
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947495
ID information
  • DOI : 10.21037/jtd-20-2602
  • Pubmed ID : 33717580
  • Pubmed Central ID : PMC7947495

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