Seoul National University researchers identify bile duct cancer evolutionary pathways

Researchers at Seoul National University Bundang Hospital have identified the genomic evolutionary pathways of cholangiocarcinoma (bile duct cancer), spanning from pre-cancerous stages to recurrence and metastasis. The study, published in ‘npj Precision Oncology’, utilized whole-exome sequencing on 72 samples from 17 patients to map the lineage of cancer cell clones.

The findings reveal that key genetic mutations, such as TP53, KRAS, and SMAD4, occur during the pre-cancerous stage. The researchers observed a ‘selective sweep’ phenomenon, where specific cell groups that are more advantageous for survival outcompete others to become primary tumors.

Crucially, the study challenges the conventional belief that cancer recurrence is caused by the regrowth of a single hidden cell. Instead, the data suggests a ‘polyclonal’ mechanism, where multiple cell groups from the original tumor reappear together during recurrence. Additionally, the research noted that while chemotherapy can leave evolutionary traces in metastatic cells, certain targetable mutations like ERBB2 amplification and KRAS remain stable, highlighting the importance of precision genomic analysis for developing effective treatment strategies.