Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing
A partir d'échantillons de tissu dysplasique et de tissu tumoral prélevés sur 45 patients atteints d'un carcinome épidermoïde de l'œsophage, puis de 21 échantillons de tissu dysplasique prélevés sur 13 patients sans carcinome, cette étude identifie la présence, dans les échantillons de tissu dysplasique, d'un ensemble d'anomalies génomiques fréquemment observées dans les carcinomes
Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the ‘two-hit’ event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC.