Allelic imbalance regions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellular carcinoma: comparison between matched primary and metastatic lesions in 22 patients by genome-wide microsatellite analysis.
To understand the molecular mechanisms of metastasis in hepatocellular carcinoma (HCC), it is necessary to identify the accumulating genetic alterations during its progression as well as those responsible for the acquisition of metastatic potential in cancer cells. In our previous study, using comparative genomic hybridization (CGH), we found that loss on chromosome 8p is more frequent in metastatic lesions than in matched primary tumors of HCC. Thus, 8p deletion might contribute to HCC metastasis. To narrow the location of metastasis-related alteration regions, we analyzed 22 primary and matched metastatic lesions of HCC by genome-wide microsatellite analysis. Common regions with high levels of allelic imbalance (AI) were identified on 17p, 8p11-cen, 8p21-23, 4q32-qter, 4q13-23, 16q, and 1p33. Regions with increased AI in metastatic lesions were 8p23.3, 8p11.2, 17p11.2-13.3, 4q21-22, 4q32-qter, 8q24.1, 9p11, 9q31, 11q23.1, 13q14.1-31, 13q32-qter, 16p13.3, 16q13, 16q22, and 19p13.1, and these were considered to be related to the metastasis phenotype. Among them, loss on 8p was again proved to be related to progression and metastasis of HCC, and 8p23.3 and 8p11.2 were two likely regions harboring metastasis-related genes. It was also shown for the first time in HCC that AI of 19p13.1 might also be related to metastatic potential. These results provide some candidate regions for further study to identify putative genes suppressing metastasis of HCC.
Liver Cancer Institute, Fudan University, 136 Yi Xue Yuan Road, 200032, Shanghai, China.
Lian-Hai
LH
Zhang
Lun-Xiu
LX
Qin
Zeng-Chen
ZC
Ma
Sheng-Long
SL
Ye
Yin-Kun
YK
Liu
Qing-Hai
QH
Ye
Xin
X
Wu
Wei
W
Huang
Zhao-You
ZY
Tang
D000328:Adult; D000368:Aged; D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000556:secondary*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction