22q11-q13 as a hot spot for prediction of disease-free survival in bile duct cancer: integrative analysis of copy number variations.
The cytogenetic pathogenesis of bile duct cancer is poorly understood. Array comparative genomic hybridization was performed on samples obtained from 24 patients with bile duct cancer and 10 normal healthy controls. Bile duct cancer patients had means of 21.8 gains and 19.2 losses of genes. We identified 20 novel copy number variation (CNV) regions that differed significantly between bile duct cancer patients and normal controls. Significant gains of copy number were observed at 2p11.2, 5p15.33, 22q11.21, 22q11.22, 22q11.23, 22q12.2, 22q12.3, 22q13.1, 22q13.31, and 22q13.33 and significant losses of copy number were observed at 8q11.21, 10q26.3, 11p15.4, 18q21.31, and 18q23. These loci included 153 genes, with 65% located at 22q11-q13. Oncostatin M signaling via the JAK/STAT pathway was the most relevant pathway, with immunohistochemical staining showing that OSM and LIF, both included in this pathway, were overexpressed in tumors. Copy number gains at 5p15.33 and 22q13.33 were correlated with early systemic recurrence in the bile duct cancer patients. In conclusion, copy number gains at 22q11-q13 were the most frequent and were correlated with poor disease-free survival. In-depth investigations are required to determine whether chromosomal aberrations at this locus are genetic markers of patient prognosis.
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Mee Joo
MJ
Kang
Department of Statistics, Seoul National University College of Natural Sciences, Seoul, South Korea.
Jayoun
J
Kim
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: jangjy4@snu.ac.kr.
Jin-Young
JY
Jang
Department of Statistics, Seoul National University College of Natural Sciences, Seoul, South Korea.
Taesung
T
Park
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Kyoung Bun
KB
Lee
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Sun-Whe
SW
Kim
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D002892:Chromosomes, Human, Pair 22; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D018628:Gene Dosage; D006801:Humans
Bile duct; cancer; cholangiocarcinoma; copy number variation; prognosis