Identification of Four Distinct Regions of Allelic Imbalances on Chromosome 1 by the Combined Comparative Genomic Hybridization and Microsatellite Analysis on Hepatocellular Carcinoma

Abstract

Frequent chromosome 1 abnormalities detected in human hepatocellular carcinoma have been implicated in early genetic events of liver carcinogenesis. Recurrent loss of 1p with a common deleted region 1p36 -p34 has been reported from microsatellite analysis, whereas common gain of the whole chromosome q-arm was described from several comparative genomic hybridization studies. The relationships between copy number changes and allelic status however remains unclear. In this study, we have conducted a simultaneous comparative genomic hybridization and microsatellite analysis study on chromosome 1 in 31 hepatocellular carcinoma cases. Microsatellite analysis revealed frequent loss of heterozygosity on 1p at loci D1S468 (74%), D1S450 (67%), D1S2667 (65%), D1S2697 (75%), D1S199 (52%), and D1S234 (67%) corresponded to the distal 1p36 region and coincided with 12 cases (86%) that presented losses on 1p by comparative genomic hybridization analysis. Although comparative genomic hybridization indicated a common deleted region of 1p36 -p35 in the current series, microsatellite analysis has refined the smallest overlapping region (SOR) to 1p36.13-p36.22. Gain of 1q as revealed by comparative genomic hybridization suggested low and high-level gains, and cases that displayed an amplicon below the heterochromatic region 1q21-q25. Common allelic imbalances of polymorphic markers D1S2635 (64%), D1S484 (67%), D1S2878 (65%), D1S196 (70%), D1S249 (64%) D1S2785 (75%), D1S2842 (73%) and D1S2836 (74%) that corresponded to the regions 1q23.1-q24.2, 1q32.1 and 1q43-q44 were detected. Three distinct regions of allelic imbalances were thus suggested on recurring 1q gain found in hepatocellular carcinoma. Furthermore, microsatellite analysis has enabled a mapping of common overrepresented regions and suggested SOR on 1q23.1-q23.3 (D1S2635-D1S2878), 1q25.1-q31.1 (D1S452-D1S238), and 1q43 (D1S2785-D1S2842). Our current study has refined chromosome 1 aberrations in hepatocellular carcinoma to four regions of allelic imbalances. The SORs delineated should provide basis for further molecular investigation in hepatocarcinogenesis on genes residing on these chromosomal regions.

Fibrolamellar carcinomas show overexpression of genes in the RAS, MAPK, PIK3, and xenobiotic degradation pathways

“…Positional mapping of typical HCC has further narrowed the regions of interest for the 1q oncogene:1q21-q22 [14], 1q23.1-q24.2 [5], 1q32.1 [5], and 1q43-q44 [5]. Our findings further point to the region of chromosome 1q23.1 as the likely critical region containing an important oncogene.…”

“…This chromosome 1q region is also frequently gained in typical HCC and is widely thought to contain an oncogene(s). Additional studies of typical HCC have further narrowed down the likely regions that contain an oncogene to include 1q21-23 and 1q42 [5].…”

Microsatellite Alterations on Chromosome 8 of Hepatocellular Carcinoma

“…In this study, it is found that the phenotyping was obviously distinct from LOH in 19.6% (11/56) of all cases examined, identified when greater difference is seen in the relative allele intensity ratio between the tumor DNA and normal DNA. This phenomenon was recently reported and much less is known about its significance [22] . It is not known that an unique instability phenotyping or a sub-type of LOH and MSI, but additional studies are needed.…”

ASPM Is a Novel Marker for Vascular Invasion, Early Recurrence, and Poor Prognosis of Hepatocellular Carcinoma

“…Using differential display analysis of gene expression profile of hepatocelllular carcinoma (HCC), we found frequent overexpression of ASPM, which is located at chromosome 1q31, a region with frequent gain in HCC (25,26). In this study, we showed that ASPM was often overexpressed in human HCC and associated with tumor progression, early tumor recurrence (ETR), and poor prognosis.…”