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Loss of 17p is one of the most frequent chromosomal alterations in primary hepatocellular carcinoma (HCC). In the present study, the association between loss of 17p and TP53 mutation was analyzed in 94 primary HCC of Chinese patients. Loss of one allele at 17p13.3 distal to the TP53 gene was observed in 48 of 94 HCC (51%), whereas loss of heterozygosity (LOH) at 17p13.1 near the TP53 gene was detected in 30 of 94 HCC (32%) and TP53 mutation was detected in only 22 of 94 HCC (23%). High frequency of LOH at 17p13.3 and relatively low frequency of TP53 mutation in the present study indicate that loss of function of a putative tumor suppressor gene at 17p13.3 may play a more important role than TP53 in HCC development. [Copyright &y& Elsevier]

Deletion of 6q is one of the most frequent chromosomal alterations in human malignant melanoma. Recently, we used chromosome painting probes of 6p and 6q to study 21 melanoma cell lines. A reciprocal translocation between chromosomes 6q and 17p was detected in one cell line (UACC-930). Upon further characterization of the translocation marker using the micro fluorescence in situ hybridization (FISH) technique, a complex rearrangement including an inversion of 6q and a translocation between the inverted 6q and 17p, [der(6)inv(6)(q16q27)t(6;17)(q26;p13)], was detected. A yeast artificial chromosome (YAC) clone spanning the breakpoint at 6q16 was isolated by the FISH screen. Loss of one or more copies of the YAC clone was also detected in 10 of 12 melanoma cell lines. This result implies that the YAC clone may contain a putative tumor suppressor gene related to the pathogenesis of malignant melanoma. Further characterizations of the breakpoint at 6q16 and molecular cloning breakpoints at 6q27 and 17p13 are in progress. [Copyright &y& Elsevier]

Abstract: Amplification of chromosome arms 3q and 5p and deletion of 3p were frequently detected in nasopharyngeal carcinoma (NPC) with comparative genomic hybridization and loss of heterozygosity studies. To identify the minimal amplified or deleted regions in these arms, structural aberrations in chromosome arms 3p, 3q, and 5p in two NPC cell lines, CNE1 and SUNE1, were studied with multiplex-color FISH (M-FISH) and chromosome region-specific probes (CRP). All CRPs, which were generated from microdissected DNA, were specific and strong in intensity, and sensitive enough to detect chromosome aberrations including translocations, deletions, and amplifications of target regions. In these two NPC cell lines, minimal regions of deletion and amplification were found at 3p12 and 3q26∼q27, respectively. On 5p, most of the regions were amplified as intact copies. Interregion translocations of these three arms were also observed. The amplification on 3q26∼q27 provided useful hints for further screening the minimal amplification at RP11-115J24 (3q26.2), containing candidate oncogene eIF-5A2. M-FISH with CRPs is thus not only useful in revealing a comprehensive picture of structural aberrations in target chromosomes, but also in narrowing down the minimal region for screening cancer-related genes. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with a very poor prognosis that has been associated with tumor metastasis. The molecular mechanism of HCC metastasis is still unclear. In this study, we established cell lines from a primary tumor (H2-P) and its metastatis (H2-M). G-banding karyotyping, comparative genomic hybridization, and fluorescence in situ hybridization were applied to study these two cell lines and the results demonstrated that they are of the same origin. These cell lines provide a very useful tool to identify genetic alterations associated with HCC metastasis. [Copyright &y& Elsevier]

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The incidence of CRC in the Chinese population has increased dramatically during the last two decades; however, nonrandom chromosomal alterations in Chinese patients have not been described. In the present study, comparative genomic hybridization (CGH) was applied to detect recurrent chromosome alterations in 26 primary colorectal carcinomas and 21 colorectal adenomas from Chinese patients. In CRC, several recurrent chromosomal changes were found, including gains of 8q (14/26 cases, 54%), 20q (54%), 3q (50%), 13q (50%), 5p (46%), 7p (42%), 7q (42%), and 12p (38%) and losses of 18q (65%) and 17p (42%). From comparison with previous CGH studies, the frequent gains of 3q and 12p might be distinctive occurrences in Chinese patients. The distribution of frequently found chromosomal alterations in different locations was studied. The gain of 20q was more frequently found in colon cancer (P<0.01) and the gain of 12p was more frequently found in rectal cancer. Chromosomal alterations were found in 19/21 of adenomas; the most frequent chromosomal alteration was the loss of 18q (9/21 cases, 43%). These recurrent alterations provide several starting points for the isolation of candidate oncogenes and tumor suppressor genes. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with a poor prognosis. Recently, we established a HCC cell line from a metastatic HCC tumor. GTG banding analysis was performed and the karyotype showed that this metastatic HCC cell line is a hypertriploid (71–78 chromosomes) with a large marker chromosome containing a long homogeneously staining region (hsr). Comparative genomic hybridization was applied to characterize the chromosomal alterations in this metastatic HCC cell line. The results showed that the hsr was composed of amplified DNA sequences from 11q13. Further characterization of the hsr may lead to the isolation of the putative amplified oncogene at 11q13. [Copyright &y& Elsevier]

Ovarian cancer is one of the most frequent gynecological malignancies worldwide with a poor prognosis. Comparative genomic hybridization has been applied to detect recurrent chromosome alterations in 31 primary ovarian carcinomas in Chinese women. Several nonrandom chromosomal changes were identified including gains of 3q (17 cases, 55%) with a minimum region at 3q25∼q26, 8q (16 cases, 52%), 19q (12 cases, 39%), Xq (11 cases, 35%), 1q (10 cases, 32%), 12p12∼q13 (10 cases, 32%), 17q (10 cases, 32%) with a minimum gain region at 17q21, and 20q (9 cases, 29%); and losses of 16q (9 cases, 29%), 1p (7 cases, 23%), 18q (7 cases, 23%), and 22 (7 cases, 23%). High-copy-number amplification was detected in eleven cases. Amplification of 3q25∼q26 was detected in four cases, and amplifications of 8q24 and 12p11.2∼q12 were observed in three cases each. The recurrent gains and losses of chromosomal regions identified in this study provide candidate regions that may contain oncogenes or tumor suppressor genes involved in the development and progression of ovarian cancer. [Copyright &y& Elsevier]