Correlating genomic copy number alterations with clinicopathologic findings in 75 cases of hepatocellular carcinoma

Abstract

Background Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. Methods aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means. Results The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly correlated with worst prognosis. Conclusions These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.

The Role of Human Satellite III (1q12) Copy Number Variation in the Adaptive Response during Aging, Stress, and Pathology: A Pendulum Model

“…Somatic copy number alterations were analyzed using comparative genomic hybridization (CGH) in 75 cases of hepatocellular carcinoma in China. The most common alterations involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%) and losses of 8p and 13q (30%) [81]. These findings corroborate an early study of 36 histologically confirmed samples of hepatocellular carcinoma, of which 1q copy gain with a 1q12 breakpoint was detected in 23 cases.…”

Cytogenomic Characterization of Giant Ring or Rod Marker Chromosome in Four Cases of Well-Differentiated and Dedifferentiated Liposarcoma

“…Cytogenetic analysis was performed on GTG banded metaphase chromosomes prepared from cultured tumor cells following the laboratory's standardized protocols; twenty metaphases were analyzed for each sample, and clonal abnormalities were karyotyped [ 17 , 18 ]. aCGH analysis using Agilent SurePrint Human Genome Microarray 4 × 60 K kit and Agilent DNA Analytical (version 4.0) (Agilent Technologies Inc., Santa Clara, CA) to detect SCNAs on genomic DNAs extracted from cultured tumor cells was performed as previously described [ 19 , 20 ]. Log2 ratio (L2R) from the tumor DNA over control DNA was used to measure the copy numbers of SCNAs.…”

Combined Assay of rDNA and SatIII Copy Numbers as an Individual Profile of Stress Resistance, Longevity, Fertility and Disease Predisposition

“…Whole-genome sequencing data have revealed that human SatII copy gain is a common phenomenon in primary human colon and kidney tumors [ 63 ]. Indirect evidence for somatic satellite expansion during tumor growth was obtained in comparative genomic hybridization (CGH) studies on 75 cases of hepatocellular carcinoma (HCG) in China [ 64 ], another 36 histologically confirmed Chinese HCG cases [ 65 ] and 33 gastric cancer patients in Saudi Arabia [ 66 ], as well as studies on lymphoma and myeloma [ 67 ] and HCG related to the hepatitis B virus [ 68 ]. Each of them yielded cytologic evidence for the overrepresentation of 1q region (1q12 locus) constituted by satellite repeats, thus suggesting SatIII expansion in cancers.…”