Introduction : Intrahepatic cholangiocarcinoma (IHC) is the second most common primary liver cancer. There is no clinical consensus for the management of multiple tumors in the intrahepatic cholangiocarcinoma. The aim of this study is to evaluate the spatio-temporal evolutions of multiple tumors that belong to the same patients and provide the clinically relevant evidence for precision therapeutic strategies in the intrahepatic cholangiocarcinoma.

Methods : A total of 34 tumors from nine patients were analyzed by next-generation sequencing using custom-designed targeted gene panel with the deep targeted platform. Single nucleotide variants with indel aberration, somatic mutations, and copy number alterations were obtained from bioinformatics computational analysis.

Results : All multiple tumors in each patient showed the significant similarity of somatic mutation with indel pattern and copy number alteration. The analysis for spatio-temporal evolution using clustering cancer evolutionary trees revealed that 8 out of 9 patients have multiple tumors from genetically same clonal origin even in different anatomical locations of the liver. We identified shared driver mutations in each patient such as BAP1, IDH1, and BRAF. The only patient not having shared non-synonymous somatic mutation showed a significantly concordant pattern of copy number alteration in multiple tumors.

Conclusions : Genomic profiles were concordant among all tumors in each patient, suggesting a common progenitor cell origin regardless of the location in the liver. Most of the patients were identified to share the actionable genetic alteration commonly in multiple tumors. Our results support the development of molecular-targeted therapeutic strategies in multifocal intrahepatic cholangiocarcinoma.