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Sequencing benign, precancerous and cancerous patches from the same gallbladders showed two ways cancer arises: the textbook stepwise route through adenoma and dysplasia, and an early split in which the cancer evolves on its own after heavy chromosome loss.
Whole-exome sequencing was performed on co-existing low-grade biliary intraepithelial neoplasia (adenoma), high-grade BilIN and carcinoma lesions, and normal tissues, from the same patients. Ageing was identified as a major factor contributing to accumulated mutations, and CTNNB1 mutations played a critical role in these tumours.
Two distinct carcinoma evolutionary paths were revealed: carcinoma can either diverge earlier and evolve more independently, or form through the classic adenoma or dysplasia to carcinoma sequence. Extensive loss of heterozygosity and mutation events in the initial stage tended to result in a cancerous niche, leading to the subsequent BilIN-independent path.
Molecular confirmation that the visible precursor is not always the parent of the cancer beside it, which tempers hopes that finding and removing dysplasia catches every tumour, and puts Wnt signalling through CTNNB1 at the start of the raised route.
Shares Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer, Dysplasia (pre-cancerous change), Gallbladder cancer.
Shares Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer, Dysplasia (pre-cancerous change), CTNNB1, Gallbladder cancer.
Shares Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer, Dysplasia (pre-cancerous change), Gallbladder cancer.
Shares CTNNB1, Nature Communications, Wnt / β-catenin, Gallbladder cancer.
Shares Dysplasia (pre-cancerous change), Gallbladder cancer.
Shares CTNNB1, Wnt / β-catenin.
Shares Nature Communications, Wnt / β-catenin.
Shares Nature Communications, Wnt / β-catenin.