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• W4313207615 abstract "We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was ERBB2 and TP53 (54.5%), followed by FBXW7 (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as SMAD4 , ROBO1 , and DICER1 . In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors." @default.
• W4313207615 created "2023-01-06" @default.
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• W4313207615 date "2022-12-08" @default.
• W4313207615 modified "2023-10-18" @default.
• W4313207615 title "Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors" @default.
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• W4313207615 doi "https://doi.org/10.7554/elife.78636" @default.
• W4313207615 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36476508" @default.
• W4313207615 hasPublicationYear "2022" @default.
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