ArticleJCO precision oncology2024
Concordance in Oncogenic Alterations Between the Primary Tumor and Advanced Disease: Insights Into the Heterogeneity of Intrahepatic Cholangiocarcinoma.
Article in JCO precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- MAPK Pathway Mutations Emerge in Mutant IDH1 Inhibitor-Resistant Cholangiocarcinoma and Attenuate the IFN Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- A Novel Approach to Quantify Heterogeneity of Intrahepatic Cholangiocarcinoma: The Hidden-Genome Classifier.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Extrahepatic Cholangiocarcinoma: Genomic Variables Associated With Anatomic Location and Outcome.JCO precision oncology · 2024Article
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23 authors.
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Abstract
purposeIntrahepatic cholangiocarcinoma (ICCA) is characterized by significant phenotypic and clinical heterogeneities and poor response to systemic therapy, potentially related to underlying heterogeneity in oncogenic alterations. We aimed to characterize the genomic heterogeneity between primary tumors and advanced disease in patients with ICCA.
methodsBiopsy-proven CCA specimens (primary tumor and paired advanced disease [metastatic disease, progressive disease on systemic therapy, or postoperative recurrence]) from two institutions were subjected to targeted next-generation sequencing. Overall concordance (oncogenic driver mutations, copy number alterations, and fusion events) and mutational concordance (only oncogenic mutations) were compared across paired samples. A subgroup analysis was performed on the basis of exposure to systemic therapy. Patients with extrahepatic CCA (ECCA) were included as a comparison group.
resultsSample pairs from 65 patients with ICCA (n = 54) and ECCA (n = 11) were analyzed. The median time between sample collection was 19.6 months (range, 2.7-122.9). For the entire cohort, the overall oncogenic concordance was 49% and the mutational concordance was 62% between primary and advanced disease samples. Subgroup analyses of ICCA and ECCA revealed overall/mutational concordance rates of 47%/58% and 60%/84%, respectively. Oncogenic concordance was similarly low for pairs exposed to systemic therapy between sample collections (n = 50, 53% overall, 68% mutational). In patients treated with targeted therapy for
conclusionThe results reflect a high degree of heterogeneity in ICCA and argue for reassessment of the dominant driver mutations with change in disease status.
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