Allelic loss of chromosome 4q21≈23 associates with hepatitis B virus-related hepatocarcinogenesis and elevated alpha-fetoprotein

Shiou Hwei Yeh, Ming Wei Lin, Shu Fen Lu, Dai Chen Wu, Shih Feng Tsai, Ching Yi Tsai, Ming Yang Lai, Hey Chi Hsu, Ding Shinn Chen, Pei Jer Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Allelic loss of chromosome 4q is one of the most frequent genetic aberrations found in human hepatocellular carcinoma (HCC) and suggests the presence of putative tumor suppressor genes within this region. To precisely define the region containing these tumor suppressor genes for further positional cloning, we tried a detailed deletion mapping strategy in 149 HCCs by using 49 microsatellite markers covering 4q12≈25. A common region with allelic loss has been identified based on the interstitial deletions occurring within it; this region is found between D4S1534 and D4S1572 (a 17.5-cM genetic interval). When we included all cases with limited aberration regions for comparison, 2 smaller regions were derived: 1 between D4S1534 and D4S2460 (3.52 cM) and 1 between D4S2433 and D4S1572 (8.44 cM). A few candidate genes were found to be down-regulated in HCCs, but without sequence mutations. In these HCCs, 4q alleleic loss was associated with hepatitis B virus infection status and the elevation of serum alpha-fetoprotein (≥400 ng/mL). In conclusion, the current study not only mapped a common allelic loss region on chromosome 4q, but it also revealed that its loss may be involved in hepatitis B virus-related hepatocarcinogenesis and the elevation of serum alpha-fetoprotein.

Original languageEnglish
Pages (from-to)847-854
Number of pages8
JournalHepatology
Volume40
Issue number4
DOIs
StatePublished - Oct 2004

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