Identification of a 1-cM region of common deletion on 4q35 associated with progression of hepatocellular carcinoma

Abstract

To identify the location of one or more of the putative tumor suppressor genes (TSG) on chromosome arm 4q that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs for their patterns of allelic loss at 39 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 71 (74%) HCCs. Detailed deletion mapping identified two distinct commonly deleted regions; one was located within a 1‐cM interval flanked by D4S1534 and D4S2929 at 4q21–22, the other in the 1‐cM interval flanked by D4S2921 and D4S2930 at 4q35. Of the tumors for which clinical data were available, allelic loss at 4q35 was more frequent in poorly or moderately differentiated tumors than in well‐differentiated tumors (3/15, 20%, vs. 14/21, 67%, P = 0.008); in tumors larger than 2 cm in size (2/11, 18%, vs. 34/62, 55%, P = 0.046); and in tumors that arose from liver cirrhosis as opposed to HCCs arising from chronic hepatitis (25/42, 60%, vs. 9/27, 33%, P = 0.048). The association of allelic losses on 4q35 with larger tumor size and aggressive histological type implies that loss or inactivation of TSG located within the 1‐cM interval of 4q35 identified here contribute to progression of HCCs. Genes Chromosomes Cancer 25:284–289, 1999. © 1999 Wiley‐Liss, Inc.

Y chromosome loss and other genomic alterations in hepatocellular carcinoma cell lines analyzed by CGH and CGH array

“…Losses of 4q and 16q were also a common occurrence in primary HCC tissues. The chromosome region 4q13~q34 contains tumor suppressor genes like SMAD1, FAT, and AREG [30]. The chromosome region 16q22.1 contains E-cadherin tumor suppressor gene [7].…”

Down-Regulation of Annexin A10 in Hepatocellular Carcinoma Is Associated with Vascular Invasion, Early Recurrence, and Poor Prognosis in Synergy with p53 Mutation

“…31 Chromosome 4q is one of the most common regions with a high frequency of allelic loss in HCC. [33][34][35]47 Chromosomal alterations at 4q are of great interest because it is a unique trait for HCC, 32,33 and chromosome 4q contains genes encoding growth factors or genes expressed predominantly in the liver. These include albumin, alcohol dehydrogenase (ADH3), fibrinogen, AFP, and UDP-glucuronyl-transferase.…”

“…31 Chromosome 4q is one of the most common regions with a high frequency of allelic loss in HCC. [32][33][34][35] Introduction of normal human chromosome 4 leads to suppressed tumorigenicity of teratocarcinoma PA-1 cells in nude mice, suggestive of a putative tumor suppressor gene on chromosome 4. 35 The biological function of ANXA10 and its role in HCC are not known.…”

The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors

“…Shoko Yoshida · Koichi Fukino · Haruhito Harada Hisaki Nagai · Issei Imoto · Johji Inazawa Hiroshi Takahashi · Akira Teramoto · Mitsuru Emi (Simons et al 1999), esophageal adenocarcinomas (Rumpel et al 1999), and oral squamous cell carcinomas (Wang et al 1999); we ourselves have defined a 1-cM region at chromosome 4q21-22 that is commonly deleted in hepatocellular carcinomas (Bando et al 1999).…”