[A preliminary report on two distinct tumor-suppressor regions on chromosome 1p36.2-p36.3 in human hepatocellular carcinomas].
OBJECTIVE
Both cytogenetic and molecular genetic analyses have unveiled non-random genomic alterations in the distal short arm of human chromosome 1 associated with a number of human malignancies including heptatocellular carcinoma (HCC). The aim of this investigation is to determine the precise region of deletion that may harbor the putative tumor suppressor genes in HCC.


METHODS
For the study of the loss of heterozygosity (LOH), 38 cases of hepatitis B virus (HBV) associated HCC and their corresponding non-tumor liver tissues were detected with 43 microsatellite polymorphic markers particularly focusing on 1p.


RESULTS
Twenty-eight of the 38 (74%) tumors showed LOH on at least one locus on 1p36.2-p36.3. Two distinct smallest common deleted regions (SCDRs) with different patterns of deletion were identified. The first SCDR is located on locus D1S2795 at 1p36.3, between loci D1S2145 and D1S2893. The second SCDR is located at 1p36.2, between loci D1S244 and D1S489. Both of the SCDRs have not been previously described in HCC. In addition, a region of possible homozygous deletion (HD) was also detected within the second SCDR between loci D1S1597 and D1S489 by comparative multiplex PCR. This is the first observation of a possible homozygous deletion on the distal short arm of chromosome 1 in HCC as well as in human tumors.


CONCLUSIONS
The high-resolution deletion mapping of 1p36.2-p36.3 in HCC in this study confirmed the presence of two distinct regions of deletion. Our data strongly suggest the presence of at least two tumor suppressor regions on 1p36.2-p36.3 and play an important role in the pathogenesis of HBV associated HCC. These results also provide a basis for further studies directed at cloning potential tumor suppressor genes in these regions.
Li
H
H
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Liew
C
C
Ding
M
M
Leow
C
C
Wang
X
X
Lau
W J
WJ
Wu
S
S
Lee
C K
CK
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats