Next generation sequencing of stage IV squamous cell lung cancers reveals an association of PI3K aberrations and evidence of clonal heterogeneity in patients with brain metastases
A partir d'échantillons tumoraux prélevés sur 79 patients atteints d'un cancer épidermoïde du poumon de stade IV, cette étude identifie, chez les patients ayant développé des métastases cérébrales, des anomalies d'expression de PI3K, la perte d'expression du gène PTEN et une hétérogénéité clonale entre les tumeurs primitives et les métastases
Large-scale genomic characterization of squamous cell lung cancers (SQCLC) has revealed several putative oncogenic drivers. There are, however, little data to suggest that these alterations have clinical relevance. We performed comprehensive genomic profiling of 79 stage IV SQCLCs (including next-generation sequencing) and analyzed differences in the clinical characteristics of two major SQCLC subtypes: FGFR1 amplified and PI3K aberrant. Patients with PI3K aberrant tumors had aggressive disease marked by worse survival (median OS 8.6 vs. 19.1 mo, p<0.001), higher metastatic burden (>3 organs 18% vs. 3%, p=0.025), and greater incidence of brain metastases (27% vs. 0% in others, p<0.001). We performed whole-exome and RNA sequencing on paired brain metastases and primary lung cancers to elucidate the metastatic process to brain. SQCLC primaries that gave rise to brain metastases exhibited truncal PTEN loss. SQCLC brain metastases exhibited a high degree of genetic heterogeneity and evidence of clonal differences between their primary sites.