Research press release


Nature Genetics

Cancer: Genetic signatures of lung cancer specific to non-smokers identified



今回、Maria Teresa Landiたちは、喫煙歴のない肺がん患者232人(診断時の平均年齢は64.8歳、75.4%が女性)の腫瘍のゲノム塩基配列を解読して、非喫煙者のがんに特異的な遺伝的パターンを明らかにした。これらの腫瘍は、ゲノム変化に基づいて3つの大きなカテゴリー(サブタイプ)に分類できた。その中には、急速に腫瘍形成が起きるものもあれば、非常にゆっくりのものもあった。サブタイプの指標としては、変異負荷の低さ、腫瘍内不均一性の高さ、特異的な染色体変化、EGFR遺伝子の高頻度変異、全ゲノム重複などがある。非喫煙者の肺がん患者におけるこの3つのサブタイプの頻度は、喫煙者での頻度とは異なるので、今回の知見は精密医療にとって有益な情報となる可能性がある。Landiたちはまた、非喫煙者の肺がん患者には、明確な喫煙関連変異パターンは見られず、そのことは副流煙にさらされた人においても同様であることを明らかにした。


Distinct patterns of mutations underlie lung cancer when it occurs in smokers versus non-smokers, according to a paper published in Nature Genetics. These findings have potential implications for the treatment of different lung cancers, as well as providing information about the genomic consequences of damage from internal processes leading to tumor formation.

Approximately 10–25% of lung cancers occur in non-smokers; however, most genome sequencing studies of lung cancer have been performed on tumors from smokers. Although secondhand tobacco smoke is often assumed to promote cancer by a similar mechanism to smoking, there is little information about this at the genomic level.

Maria Teresa Landi and colleagues sequenced tumors from 232 patients (mean age at diagnosis was 64.8 years old; 75.4% were female) with lung cancer who had never previously smoked in order to identify genetic patterns that were specific to cancers in non-smokers. The tumors could be classified into three broad categories based on genomic changes, some of which developed rapidly while others developed slowly. Features that characterize these subtypes included low mutation burden with high intra-tumor heterogeneity, specific chromosomal alterations and high frequency of mutations in the EGFR gene and whole-genome doubling. These three subtypes are seen at different frequencies in tobacco-smoking patients with lung cancer and as such, could inform precision therapy. The authors also found that no strong genetic signatures of tobacco smoking were identified in this study, even in individuals who had been exposed to secondhand tobacco smoke.

Although replication in larger patient cohorts is needed to characterize these results definitively, the authors conclude that these findings could take us one step closer to the personalized treatment of lung cancer in non-smokers.

doi: 10.1038/s41588-021-00920-0


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