Genome-wide single nucleotide polymorphism array analysis reveals recurrent genomic alterations associated with histopathologic features in intrahepatic cholangiocarcinoma.
Recent studies indicate that genomic alterations (GAs) are associated with many human malignancies. Genome-wide analysis of GAs involved in intrahepatic cholangiocarcinoma (ICC) and association with histopathologic features are limited. To help characterize this relatively rare neoplasm, we collected 32 frozen tissue samples of ICC to study GAs and molecular karyotypes by using single-nucleotide polymorphism array. Recurrent GAs occurring in at least 40% of the patients were further correlated with histopathologic features. Gain of 1q21.3-q23.1 and losses of 1p36.33-p35.3 and 3p26.3-p13 were significantly associated with larger tumor size more than 5 cm in diameter; and loss of 4q13.2-q35.2 with tumor multiplicity. Moreover, losses of 1p36.32-p35.3, 3p26.3-p22.2, 4q13.1-q21.23, 4q31.3-q34.3 and 4q34.3-35.2 were inclined to be associated with high histological grade. As to tumor vascular invasion, gain of 1q21.3-q23.1 and losses of 3p22.1-p12.3 and 4q13.2-q35.2 were significantly associated with tumor vascular invasion. Some regions were concurrently associated with multiple histopathologic characteristics, including loss of 4q13.2-q35.2 associated with larger tumor size, high histological grade and vascular invasion; losses of 1p36.33-p35.3 and 3p26.3-p22.2 with larger tumor size and high histological grade; and gain of 1q21.3-q23.1 with larger tumor size and vascular invasion. Our study indicates that complex chromosomal instability is characteristic of ICC. Detecting crucial GAs will enable risk stratification and development of personalized therapies.
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Wan-Ting
WT
Huang
Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Shao-Wen
SW
Weng
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Yu-Ching
YC
Wei
Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Huey-Ling
HL
You
Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Jui-Tzu
JT
Wang
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Hock-Liew
HL
Eng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability; D002877:Chromosomes, Human; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D047368:Tumor Burden
D014408:Biomarkers, Tumor
ICC; SNP array; whole genome analysis