JCO precision oncology · 2026
Molecular Profiling of Cholangiocarcinoma Predicts Outcomes Post-Liver Transplantation.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Connor Ashton A, Mattohti Mahinur, Kodali Sudha, Abdelrahim Maen, Elaileh Ahmed, Semaan Samar, Mobley Constance M, Simon Caroline J, Cheah Yee Lee, Saharia Ashish, Dhingra Sadhna, Schwartz Mary R, Moore Linda W, Heyne Kirk, Victor David W, Li Xian C, Vauthey Jean-Nicolas, Javle Milind, Gaber A Osama, Ghobrial R Mark
Аннотация
PURPOSE: Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Liver transplantation (LT) offers good outcomes. Tumor molecular profiling may inform peri-LT treatment.
MATERIALS AND METHODS: Patients with CCA who underwent LT at a single center between 2014 and 2021 were identified retrospectively. Next-generation sequencing (277 genes) was performed on 28 CCAs from 18 patients, including five perihilar and 24 intrahepatic tumors.
RESULTS: Mutations were reported in 45 genes, most frequently IDH1 (5 patients), BAP1 (5), and TP53 (4). BAP1 was associated with neoadjuvant treatment response. Altered genes were organized into five pathways, namely: kinase-RAS (11 patients), TP53 (9), epigenetic (8), SWI-SNF (7) and RB-cell cycle (4). Both TP53 and RB-cell cycle pathway alterations were prognostic. Tumors were clustered into three groups, named here as cell cycle (seven patients), genomic instability (6), and cell survival (5). The latter had no post-transplant deaths. In 18 serially sequenced tumors from eight patients, mutational heterogeneity over time was quantified by Jaccard Index. This reflected both external selection pressures by systemic therapies and intrinsic tumor biology, being the lowest in cell survival tumors. Pathway- and subtype-level changes were rare.
CONCLUSION: In this LT cohort, CCA molecular profiling informed prognosis and treatment response. Heterogeneity may depend on early tumorigenesis disruptions, potentially explaining outcome differences.
MATERIALS AND METHODS: Patients with CCA who underwent LT at a single center between 2014 and 2021 were identified retrospectively. Next-generation sequencing (277 genes) was performed on 28 CCAs from 18 patients, including five perihilar and 24 intrahepatic tumors.
RESULTS: Mutations were reported in 45 genes, most frequently IDH1 (5 patients), BAP1 (5), and TP53 (4). BAP1 was associated with neoadjuvant treatment response. Altered genes were organized into five pathways, namely: kinase-RAS (11 patients), TP53 (9), epigenetic (8), SWI-SNF (7) and RB-cell cycle (4). Both TP53 and RB-cell cycle pathway alterations were prognostic. Tumors were clustered into three groups, named here as cell cycle (seven patients), genomic instability (6), and cell survival (5). The latter had no post-transplant deaths. In 18 serially sequenced tumors from eight patients, mutational heterogeneity over time was quantified by Jaccard Index. This reflected both external selection pressures by systemic therapies and intrinsic tumor biology, being the lowest in cell survival tumors. Pathway- and subtype-level changes were rare.
CONCLUSION: In this LT cohort, CCA molecular profiling informed prognosis and treatment response. Heterogeneity may depend on early tumorigenesis disruptions, potentially explaining outcome differences.