Abstract
BackgroundDistinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well‐established. However, comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive.MethodsWe analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture‐based ultra‐deep sequencing of 68 lung cancer‐related genes.ResultsOf the 318 NSCLC patients, 215 were diagnosed with LUAD and 103 with LUSC. Adenocarcinoma in situ and acinar adenocarcinoma were the most predominant subtypes of LUAD. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. Among the LUAD subtypes, EGFR sensitizing mutations were most prevalent in the invasive lepidic subtype. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were also EGFR‐mutants. Patients with colloidal, invasive mucinous, and fetal subtypes had the least number of EGFR mutations. Moreover, KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. A total of 90% of the LUSC patients harbor mutations in TP53, wherein all patients except five with nonkeratinizing were TP53 mutants. PIK3CA amplifications were most prevalent in keratinizing, followed by basaloid and nonkeratinizing subtypes.ConclusionThese data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions.
Highlights
Lung cancer is the leading cause of cancer-related death in China and around the world.[1,2] Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer cases diagnosed, with two major histological types: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) accounting for nearly 50% and 30% of NSCLC, respectively.[3]
Our cohort consisted of 318 Chinese stage I-IV NSCLC patients diagnosed with either lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) from seven hospitals
To the best of our knowledge, our study is the first to use a unified strategy to compare the mutational profile of LUAD and LUSC predominant histological subtypes in Chinese NSCLC patients
Summary
Lung cancer is the leading cause of cancer-related death in China and around the world.[1,2] Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer cases diagnosed, with two major histological types: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) accounting for nearly 50% and 30% of NSCLC, respectively.[3]. Distinction in the mutational profile between the common histological types, lung adenocarcinoma (LUAD) and squamous cell lung carcinoma (LUSC) has been well-established. Comprehensive mutation profiles of the predominant histological subtypes within LUAD and LUSC remains elusive. Methods: We analyzed the mutational profile of 318 Chinese NSCLC patients of adenocarcinoma and squamous cell carcinoma predominant subtypes from seven hospitals using capture-based ultra-deep sequencing of 68 lung cancer-related genes. On the other hand, keratinizing squamous cell carcinoma was the most predominant subtype of LUSC. More than half of the patients with preinvasive adenocarcinoma in situ, minimally invasive, acinar, micropapillary and papillary subtypes were EGFR-mutants. Invasive mucinous, and fetal subtypes had the least number of EGFR mutations. KRAS mutations were prevalent in patients with invasive mucinous, colloid, enteric and solid subtypes. Conclusion: These data suggest that the mutational profiles among the predominant histological subtypes were very distinct, which provided a reliable tool to improve treatment decisions
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