Genomic copy number alterations in Korean bile duct cancer in comparison with normal healthy Korean

Abstract

Background: The cytogenetic pathogenesis of bile duct cancer is poorly understood. This study investigated changes in gene copy number in Korean bile duct cancers and compared them with that of normal healthy Koreans. Furthermore, we explored the correlation of copy number variation with the disease free survival of bile duct cancer patients. Methods: Array comparative genomic hybridization was performed on 24 Korean bile duct cancer specimens and 10 normal healthy Koreans. The results were validated by the disease free survival of bile duct cancer patients. Results: A total of 984 copy number variations (CNVs) in 306 CNV regions (CNVRs) were distributed throughout all 22 chromosomes in Korean bile duct cancer patients. Korean bile duct cancer patients had a mean of 21.8 gains and 19.2 losses and the average number of CNVR was 35.9 per patient. Frequent sites of gains were located at 22q11.22, 2p11.2-p.11.1, 14q32.33 and 17q12. Frequent site of losses were located at 19q12-q13.43. When comparing 10 normal healthy Korean controls with the 24 Korean bile duct cancer patients, a total of 7,825 CNVs and 2,081 CNVRs were identified. Twenty significant CNVRs showed significant differences between the normal healthy Koreans and the Korean bile duct cancer patients. Significant gains of copy number were observed in 2p11.2, 5p15.33, 22q11.21, 22q11.22, 22q11.23, 22q12.2, 22q12.3, 22q13.1, 22q13.31 and 22q13.33. Significant losses of copy number were observed in 8q11.21, 10q26.3, 11p15.4, 18q21.31 and 18q23. Copy number gains in 5p15.33 and 22q13.33 were correlated with early systemic recurrence in the Korean bile duct cancer patients. Conclusion: This study defined regions of the genome associated with changes in DNA copy number in Korean bile duct cancer. Copy number gain in 22q11-q13 was the most frequent in Korean bile duct cancer and was correlated to poor disease free survival. The findings have implications for identifying therapeutic targets, screening, and prognostication.