Concordance in Oncogenic Alterations Between the Primary Tumor and Advanced Disease: Insights Into the Heterogeneity of Intrahepatic Cholangiocarcinoma.

Autor:	McIntyre SM; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Preston WA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Walch H; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Sharib J; Department of Surgery, Duke University Medical Center, Durham, NC., Kundra R; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY., Sigel C; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Lidsky ME; Department of Surgery, Duke University Medical Center, Durham, NC., Allen PJ; Department of Surgery, Duke University Medical Center, Durham, NC., Morse MA; Department of Medicine, Duke University Medical Center, Durham, NC., Chen W; Department of Pathology, Duke University Medical Center, Durham, NC., Cercek A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY., Harding JJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY., Abou-Alfa GK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY., O'Reilly EM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Park W; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Graduate School of Medical Sciences, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Balachandran VP; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Drebin J; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Soares KC; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Wei A; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Kingham TP; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., D'Angelica MI; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Iacobuzio-Donahue C; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.; The David M. Rubenstein Center for Pancreatic Cancer Research, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Jarnagin WR; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2024 Feb; Vol. 8, pp. e2300534.
DOI:	10.1200/PO.23.00534
Abstrakt:	Purpose: Intrahepatic 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. Methods: Biopsy-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. Results: Sample 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 IDH1/2 alterations (n = 6) or FGFR2 fusions (n = 3), there was 100% concordance between the primary and advanced disease specimens. In two patients, FGFR2 (n = 1) and IDH1 (n = 1) alterations were detected de novo in the advanced disease specimens. Conclusion: The results reflect a high degree of heterogeneity in ICCA and argue for reassessment of the dominant driver mutations with change in disease status.
Databáze:	MEDLINE
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