Source: Sun Yat-sen University Cancer Center
Written by: Sun Yat-sen University Cancer Center
Edited by: Wang Dongmei

A research study titled “Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing” was published online on Nature Communications by Prof. Musheng Zeng’s group from Sun Yat-sen University and Prof. Fan Bai’s group from Peking University On September 12, 2017.

Esophageal cancer is the 8th most common and 6th most lethal cancer, having a 5-year survival rate as low as 15–25%. Esophageal squamous cell carcinoma (ESCC) is the dominant subtype of esophageal cancer worldwide, accounting for 90% of the cases all over the world. A notably high incidence is observed in China. The pathogenesis of ESCC is believed to be a multi-step process. At the initial stage, squamous epithelial cells exhibit nuclear atypia and abnormal maturation but do not invade through the basement membrane. This stage is known as dysplasia, and it is believed to be the precursor lesion of ESCC. From a genomic perspective, little is known about the evolving process from dysplasia to ESCC, especially how and at which stage the key carcinogenic events are acquired.

Here, Prof. Musheng Zeng’s group from Sun Yat-sen University and Prof. Fan Bai’s group from Peking University have collaborated and 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. Their 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.

This work was supported by the the grants from the National Key R&D Program, the Ministry of Science and Technology of China, the National Natural Science Foundation of China, the Science and Technology project of Guangdong Province, etc.