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Genetic Aberrations in Normal Tissues Adjacent to Biliary Tract Cancers.
Chae Hwa Kwon1, Sung Hee Park1, Hye Ji Lee1
1Biomedical Research Institute, Pusan National University Hospital, 49241 Busan, Republic of Korea.
Biomedicines
|November 27, 2025
Summary
Normal tissues near biliary tract cancer (BTC) harbor distinct early genetic changes, suggesting a role in carcinogenesis. These findings support a multistep cancer model and offer new avenues for early BTC detection.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- The role of normal adjacent tissues (NATs) in biliary tract cancer (BTC) development is poorly understood.
- Field cancerization, the presence of pre-malignant changes in tissues surrounding a tumor, is a potential factor in BTC.
Purpose of the Study:
- To investigate the genomic landscape of normal tissues adjacent to BTC.
- To determine if NATs harbor somatic mutations and their potential role in BTC carcinogenesis.
Main Methods:
- Targeted genomic profiling of tumor tissues, matched NATs, and germline DNA (leukocytes) from 13 BTC patients.
- Integration of genomic data with clinicopathological information, including inflammation and precursor lesions like biliary intraepithelial neoplasia (BilIN).
Main Results:
- Tumor tissues showed alterations in DNA damage response, cell cycle control, and oncogenic signaling pathways.
- NATs contained unique early somatic variants, distinct from tumor and germline DNA, associated with extracellular matrix-receptor interactions.
- Extrahepatic cholangiocarcinoma patients exhibited BilIN, indicating field cancerization linked to chronic inflammation.
Conclusions:
- Normal adjacent tissues in BTC are not genetically silent and contain biologically relevant somatic mutations.
- Genomic alterations in NATs, alongside inflammation and precursor lesions, support a multistep model for BTC development.
- These findings suggest potential for early BTC detection and risk stratification strategies.
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