Allelic imbalance at 1p36 in the pathogenesis of human hepatocellular carcinoma.
OBJECTIVE
It has been well accepted that there is an allelic imbalance at a subtelomeric region of chromosome 1p in various human malignancies including hepatocellular carcinoma. We conducted a detailed deletion mapping study at 1p36 loci in 65 hepatocellular carcinomas as an initial step towards positional cloning of the target gene.


METHODS
We performed a fine-scale deletion mapping using 10 highly polymorphic microsatellite markers along the telomeric region of 1p (1p32-p36.3) and compared the clinicopathologic features with allelic imbalance of 1p36 loci.


RESULTS
Allelic imbalance occurred in at least one locus on 1p in 32 (49.2%) of the 65 cases. Consequently, it was confirmed that a common region of overlaps was restricted to 1p36 and it was further clearly demonstrated that there were at least three independent regions in 1p36 (1p36.1, p36.2'36.3 and p36.3). An apparent trend towards significance has been demonstrated between allelic imbalance at 1p36 loci and tumors with classifcation T1-T2 (p<0.01).


CONCLUSIONS
The present study demonstrated that the shortest region of overlap was confined within 1p36 chromosomal sub-band in human hepatocellular carcinoma, which might be involved in an early step of hepatocarcinogenesis, and it encourages future studies to identify the putative tumor suppressor gene(s) at 1p36.
Koshikawa
Katsumi
K
Department of Surgery II, Nagoya University School of Medicine, Nagoya, Aichi, Japan. kosshi@tsuru.med.nagoya-u.ac.jp
Nomoto
Shuji
S
Yamashita
Katsuya
K
Ishigure
Kiyoshi
K
Takeda
Shin
S
Nakao
Akimasa
A
D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats