Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma

Abstract

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma

“…Using genomewide microsatellite analysis, this deletion on chromosome 8p was further proved to be related to the progression and metastasis of HCC, and 8p23.3 and 8p11.2 were two likely regions harboring metastasisrelated genes (Zhang et al, 2003). Similar results were obtained by other researchers (Li et al, 2001;Wang et al, 2001a). Besides HCC, the deletion of chromosome 8p has also been shown to play an important role in the tumor progression and metastasis of many other kinds of human malignancies, including colorectal (Takanishi et al, 1997;Parada et al, 1999), bladder (Wagner et al, 1997;Ohgaki et al, 1999;Muscheck et al, 2000), breast (Yokota et al, 1999), larynx (Kujawski et al, 1999), renal (Bissig et al, 1999), and lung (Petersen et al, 2000) cancers.…”

Gene Expression Analysis in HBV Transgenic Mouse Liver: A Model to Study Early Events Related to Hepatocarcinogenesis

“…As in other solid tumors, development, progression, and metastasis of HCC are multistep processes and are believed to be caused by the accumulation of genetic alterations, including chromo-somal aberrations, oncogene activation, and inactivation of tumor suppressor genes (33)(34)(35)(36)(37). Recent studies have identified numerous epigenetic changes, such as promoter CpG island methylation, that are responsible for inactivation of tumor suppressor genes (38)(39)(40)(41).…”

Increased expression of glycosyl‐phosphatidylinositol anchor attachment protein 1 (GPAA1) is associated with gene amplification in hepatocellular carcinoma

“…5,27 To elucidate the relation between GPAA1 gene copy number and GPAA1 overexpression, quantitative microsatellite analysis (QuMA) was performed to measure the GPAA1 copy number on DNA from 15 HCCs. Normal GPAA1 DNA copy number (range, 1.48-2.36) was observed in 4 (27%) HCCs, while 6 (40%) HCCs showed 1 to 2 DNA copy number gains (range, 2.78-3.60), and another 5 cases (33%) demonstrated high level GPAA1 amplification (range, 4.02-6.84).…”