Frequent loss of heterozygosity in two distinct regions, 8p23.1 and 8p22, in hepatocellular carcinoma

Abstract

AIM:To identify the precise location of putative tumor suppressor genes (TSGs) on the short arm of chromosome 8 in patients with hepatocellular carcinoma (HCC). METHODS:We used 16 microsatellite markers informative in Japanese patients, which were selected from 61 published markers, on 8p, to analyze the frequency of loss of heterozygosity (LOH) in each region in 33 cases (56 lesions) of HCC. RESULTS:The frequency of LOH at 8p23.2-21 with at least one marker was 63% (20/32) in the informative cases. More specifically, the frequency of LOH at 8p23.2, 8p23.1, 8p22, and 8p21 was 6%, 52%, 47%, and 13% in HCC cases. The LOH was significantly more frequent at 8p23.1 and 8p22 than the average (52% vs 22%, P = 0.0008; and 47% vs 22%, P = 0.004, respectively) or others sites, such as 8p23.2 (52% vs 6%, P = 0.003; 47% vs 22%, P = 0.004) and 8p21 (52% vs 13%, P = 0.001; 47% vs 13%, P = 0.005) in liver cancer on the basis of cases. Notably, LOH frequency was significantly higher at D8S277, D8S503, D8S1130, D8S552, D8S254 and D8S258 than at the other sites. However, no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues. CONCLUSION:Deletion of 8p, especially the loss of 8p23.1-22, is an important event in the initiation or promotion of HCC. Our results should be useful in identifying critical genes that might lie at 8p23.1-22.

Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma

“…The present study also evaluated the prevalence of LOH at 8p23.1 in HCCs, and showed its occurrence rate to be 61.29% (D8S503) or 68.4% (D8S1130) in HCCs, similar to a previous study that demonstrated the frequency of LOH at 8p23.2-21 to be 63% in HCC in a Japanese population (35). However, no significant mutation or absence of expression of the genes at 8p23.2-21 has been identified (35), and the present study also found no significant association between the frequency of LOH at 8p23.1 and the clinicopathological characteristics of HCC.…”

“…However, no significant mutation or absence of expression of the genes at 8p23.2-21 has been identified (35), and the present study also found no significant association between the frequency of LOH at 8p23.1 and the clinicopathological characteristics of HCC. Although no significant genetic alterations were detected in HCC at 8p23.1, the results of the present study suggest that unknown genes in this region may be significant in HCC, as suggested by a previous study (35). Further studies are required to explore the significance of LOH at 8p23.1 in the development of HCC.…”

“…Lu et al (35) identified two sites, 8p23.1 and 8p22, which potentially contain tumor suppressor genes involved in human liver carcinogenesis. In the present study, loss of 8p23.1 was another frequently observed locus with genomic imbalances in HGDNs, similar to the results observed in previous studies (23,24,32).…”

Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling

“…Previous studies of allelic imbalance using highdensity polymorphic markers suggest that one or more tumor suppressor loci are involved in HCC, including chromosome 8p21, 8p22, and 8p23 (21,22). Recent studies using microarray-based comparative genomic hybridization (CGH) have indicated that allelic loses occur over more extended region, such as chromosome 8p11-p23, implying that more novel tumor suppressors remain to be involved in tumor initiation and progression (23)(24)(25)(26).…”

Deletion at chromosome arms 6q16–22 and 10q22.3–23.1 associated with initiation of prostate cancer

“…The LOH at 6q16-22 and 10q22.3-23.1 tended to differ from the results of our previous allelotyping at 8p and 13q in the same samples and another type of human cancer. [21][22][23][24] These results led us to suggest that LOH at 6q16-22 and 10q22.3-23.1 might not be a newly occurring genetic change during the progression from early stage prostate cancer to clinical significant prostate cancer even in the metastatic stage. Previously, we had performed a genome-wide search for LOH with human genetic markers in several types of cancer and confirmed that chromosomal alterations, especially deletions of some restricted regions, such as 8p22-23.1 and 13q14, are not only related with the initiation but also closely associated with subsequent progression of human cancers, especially in the metastasis of primary tumors.…”