TY - JOUR

T1 - Personalized circulating tumor DNA in patients with hepatocellular carcinoma

T2 - a pilot study

AU - Pommergaard, H. C.

AU - Yde, C. W.

AU - Ahlborn, L. B.

AU - Andersen, C. L.

AU - Henriksen, T.

AU - Hasselby, J. P.

AU - Rostved, A. A.

AU - Sorensen, C. L.

AU - Rohrberg, K. S.

AU - Nielsen, F. C.

AU - Rasmussen, A.

PY - 2022

Y1 - 2022

N2 - Background Mutational analysis of circulating tumor DNA (ctDNA) can potentially be used for early detection of recurrence after resection for hepatocellular carcinoma (HCC). Mutations from tumor may be identified in plasma as an early sign of recurrence. We conducted a pilot study investigating if somatic mutations could be detected in plasma in patients undergoing liver resection for HCC and in patients with advanced non-resectable HCC. Methods and results We prospectively included patients undergoing curative liver resection for HCC. Tumor tissue was investigated with whole exome sequencing and preoperative blood samples were evaluated for ctDNA using targeted next-generation sequencing (NGS) with TruSight Oncology 500 including 523 cancer-associated genes. Subsequently, the method was evaluated in patients with advanced HCC. We included eight patients curatively resected for HCC, where tumor tissue mutations were identified in seven patients. However, only in one patient tumor specific mutations were found in the preoperative blood sample. In all three patients with advanced HCC, tumor mutations were detected in the blood. Conclusions In patients with resectable HCC, ctDNA could not be reliably detected using the applied targeted NGS method. In contrast, ctDNA was detected in all patients with advanced HCC. Small tumors, tumor heterogeneity and limited sequencing coverage may explain the lack of detectable ctDNA.

AB - Background Mutational analysis of circulating tumor DNA (ctDNA) can potentially be used for early detection of recurrence after resection for hepatocellular carcinoma (HCC). Mutations from tumor may be identified in plasma as an early sign of recurrence. We conducted a pilot study investigating if somatic mutations could be detected in plasma in patients undergoing liver resection for HCC and in patients with advanced non-resectable HCC. Methods and results We prospectively included patients undergoing curative liver resection for HCC. Tumor tissue was investigated with whole exome sequencing and preoperative blood samples were evaluated for ctDNA using targeted next-generation sequencing (NGS) with TruSight Oncology 500 including 523 cancer-associated genes. Subsequently, the method was evaluated in patients with advanced HCC. We included eight patients curatively resected for HCC, where tumor tissue mutations were identified in seven patients. However, only in one patient tumor specific mutations were found in the preoperative blood sample. In all three patients with advanced HCC, tumor mutations were detected in the blood. Conclusions In patients with resectable HCC, ctDNA could not be reliably detected using the applied targeted NGS method. In contrast, ctDNA was detected in all patients with advanced HCC. Small tumors, tumor heterogeneity and limited sequencing coverage may explain the lack of detectable ctDNA.

KW - HCC

KW - ctDNA

KW - NGS

KW - Circulating tumor DNA

KW - Liver resection

KW - HETEROGENEITY

KW - DIAGNOSIS

KW - CIRRHOSIS

KW - NODULES

KW - CANCER

U2 - 10.1007/s11033-021-06962-1

DO - 10.1007/s11033-021-06962-1

M3 - Letter

C2 - 34811635

VL - 49

SP - 1609

EP - 1616

JO - Molecular Biology Reports

JF - Molecular Biology Reports

SN - 0301-4851

IS - 2

ER -