Clinicopathological significance of loss of heterozygosity on chromosome 13q in hepatocellular carcinoma.
OBJECTIVE
Allelic loss is the most frequently genetic alteration found in hepatocellular carcinoma (HCC). Previous genome-wide studies have indicated that chromosome 13q is one of the most frequently affected chromosomes. However, reports on detailed deletion mapping as well as detailed clinicopathological correlation are scanty.


METHODS
We performed high-density allelotyping on chromosome 13q in HCC from 60 patients and investigated the correlation between allelic losses on chromosome 13q and the clinicopathological features.


RESULTS
Allelic loss at one or more of the 29 microsatellite markers was found in 28 (47%) of the 60 HCCs. Allelic losses were more frequently found in tumors with larger size or in tumors at more advanced tumor stages (P = 0.015 and 0.012, respectively). These two clinicopathological features were also significantly associated with the accumulation of allelic losses in terms of fractional allelic loss index (P = 0.028 and 0.018, respectively). In addition, subchromosomal regions located at 13q12.3-14.1 and 13q32 were found to be significantly associated with advanced tumor stages and larger tumor size, respectively (P = 0.008 and 0.007).


CONCLUSIONS
The overall findings suggested that allelic losses on 13q might play an important role in contributing to a more aggressive tumor behavior. Putative tumor suppressor genes might be harbored at 13q12.3-14.1 and 13q32, and inactivation of these genes via allelic losses might enhance tumor progression in HCC.
Departments of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
Chun Ming
CM
Wong
Joyce Man Fong
JM
Lee
Tracy Ching Man
TC
Lau
Sheung Tat
ST
Fan
Irene O L
IO
Ng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D006511:Hepatitis B Antigens / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness
D004273:DNA, Neoplasm; D006511:Hepatitis B Antigens