Fig. 6: TATs adopt two mechanisms to undergo the premalignant transformation and contribute to relapse.

One ancestral clone carrying driver mutations such as TP53 mutation proliferate to produce mucosa tissue. Some of the offspring cells gain novel driver mutations to develop into primary tumours. After resection, a some cells in TAT originated from the same ancestral clone as tumours might inherit the same driver alterations in tumours that tend to occur in an early stage of tumorigenesis, and further obtain novel mutations triggering premalignant transformation and tumour progression, leading to disease relapse. b In some other cells that inherit no identical driver mutations as in primary tumour, private mutations might be accumulated, and later contribute to the development of a second primary tumour, which is evolutionarily independent of primary tumours, resulting in disease recurrence. Notably, cells sharing identical mutations with primary tumour might still exist in the TAT simultaneously, but they failed to develop into a new tumour.