Chromosomal gains and losses are uncommon in hairy cell leukemia: a study based on comparative genomic hybridization and interphase fluorescence in situ hybridization.

In contrast to other subtypes of lymphoproliferative malignancies, the genetic mechanisms underlying the pathogenesis of hairy cell leukemia (HCL) are unknown. We studied densely infiltrated splenic tissue of 14 cases of HCL for the presence of chromosomal gains and losses by comparative genomic hybridization (CGH). Chromosomal imbalances were detected in only four of the 14 cases. Chromosomal gains involved the regions 5q13-q31 (two cases) and 1p32-p36.2 (one case). A loss of the region 11q14-q22 was found in one additional patient. The imbalances affecting the regions 5q and 11q were confirmed by interphase fluorescence in situ hybridization (FISH) using PAC clone 144G9 (5q31) and YAC clones 755B11 (11q22.3-q23.1) and 801E11 (11q22.3-q23.1 spanning the ATM gene) and occurred in 61% to 75% of analyzed nuclei. The latter DNA probes and probes hybridizing to chromosomal regions, which are frequently deleted in other subtypes of non-Hodgkin lymphomas (NHL), namely 9p21/ P16(INK4A), 13q14/D13S25, and 17p13/P53 were subsequently applied to all 14 cases of HCL, but no additional abnormalities were found. We conclude that overrepresentation of chromosome 5 represents a recurrent aberration in HCL and that the commonly overrepresented region resides in 5q13-q31. Chromosomal imbalances including deletions of the tumor suppressor gene loci 9p21/P16(INK4A), 13q14/D13S25, and 17p13/P53 rarely occur in HCL in contrast to some other subtypes of B-cell NHL. The pathogenetic role of 11q/ATM alterations in HCL remains to be determined.     

Detection of genetic alterations in advanced prostate cancer by comparative genomic hybridization

In this study, we examined nine cases of advanced Japanese prostate cancer by comparative genomic hybridization (CGH) to detect chromosomal imbalances across the entire genome and to identify several new regions likely to contain genes important to the development and progression of this disease. These cases had been previously examined for numerical chromosomal aberrations by fluorescence in situ hybridization (FISH). By CGH, the following regions were found to be over-represented (gains), with fluorescence ratio values higher than the threshold: 4p, 6p, 8q, 11q, 12q, 15q, 16p, 17q, 20, and 21 (>4 cases); underrepresentation (losses) involved: 1q, 4q, 5q, 6q, 13q, 14q, and 22 (>4 cases). The shortest regions of overlap (SRO) of gains were noted at 8q24.1 through q24.3, 12q23, and 17q23 through q24 (>5 cases). The SRO of losses were seen at 5q14 through q21, 6q16.1 through q21, 13q21.3 through q22, and 14q21 (>5 cases). Notably, the gain of chromosomes 8 and 12 by CGH was in agreement with the FISH data, suggesting that the gain of chromosomes 8 and 12 may play an important role in prostate carcinogenesis. The genes on the SRO regions were also discussed in relation to oncogenes and bone metastases.     

Analysis of genetic alterations in primary nasopharyngeal carcinoma by comparative genomic hybridization

To identify genetic alterations associated with the development and progression of human nasopharyngeal carcinoma (NPC), 57 tumors were analyzed by comparative genomic hybridization (CGH). In 47 cases, chromosomal imbalances were found. Several recurrent chromosomal abnormalities were identified in the present study. The most frequently detected chromosomal gains involved chromosome arms 12q (24 cases, 51%), 4q (17 cases, 36%), 3q (16 cases, 34%), 1q (15 cases, 32%), and 18q (15 cases, 32%). Common regions of gain involved 12q13--q15, 4q12--q21, and 3q21--q26. High-copy-number increases of chromosomal materials were detected in four chromosomal regions, 3q21--q26.2, 4p12--q21, 8p, and 12q14--q15. The most frequently detected loss of chromosomal materials involved chromosome arms 16q (26 cases, 55%), 14q (21 cases, 45%), 1p (20 cases, 43%), 3p (20 cases, 43%), 16p (19 cases, 40%), 11q (17 cases, 36%), and 19p (16 cases, 34%). The most common regions of loss involved 14q24--qter, 1pter--p36.1, 3p22--p21.3, 11q21--qter, and the distal region of 19p. Genomic alterations detected by CGH were compared and found to be largely consistent with those identified in banding analysis and loss of heterozygosity studies. However, several previously unrecognized recurrent alterations were also identified in the present study, including gain of 4q and 18q, and loss of 16q, 14q, and 19p. In addition, gain of 1q, 8q, 18q, and loss of 9q showed a statistically significant association with advanced clinical stages (P < 0.05). Identification of recurrent sites of chromosomal gain and loss identify regions of the genome that may contain oncogenes or tumor suppressor genes, respectively, which may be involved in the tumorigenesis of NPC. Published 2000 Wiley-Liss, Inc.     

Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas.

Comparative genomic hybridization (CGH) was used to search for gains, high-level amplifications and losses of DNA sequences along all chromosome arms in 19 primary Merkel cell carcinomas (MCC). Extensive genetic aberrations, with a mean value of 5.5+/-1.1 changes per tumor were detected in 13 out of the 19 samples analyzed. Our CGH results reveal several new and other previously known chromosomal regions that are involved in the pathogenesis of MCC. The majority of the alterations were gains of whole chromosomes or whole chromosome arms. Compared to losses, the frequency of DNA copy number gains was two-fold. DNA sequence copy number gains were most common in chromosomes 6 (42%), 1 (37%), and 5 (32%). The most frequent minimal common regions of gains were 6pterqter (42%), 1q11q31 (32%), and 5p (32%). No recurrent high-level amplifications were observed. High-level amplifications of small chromosomal regions were found in four samples out of the 19 tumors analyzed (21%). Amplifications affected 1q22q24 (5%), 4p (5%), and 5p (5%). Losses most frequently affected chromosomes 13 (21%) and 4 (16%). Minimal common regions with the most frequent losses were 13q13q31 (21%), 4q (16%), and 16q (11%). No significant statistical correlation between genomic aberrations and clinicopathological factors was revealed, despite the fact that there was an obvious tendency towards it. Primary MCC expressing DNA alterations were predominantly distinguished in large tumors, and risk of metastatic dissemination was three-fold compared to tumors with no DNA alterations.     

Genetic alterations in intrahepatic cholangiocarcinoma as revealed by degenerate oligonucleotide primed PCR-comparative genomic hybridization

Intrahepatic cholangiocarcinoma (ICC), a malignant neoplasm of the biliary epithelium,is usually fatal because of difficulty in early diagnosis and lack of availability of effective therapy. The genetic mechanisms involved in the development of ICC are not well understood and only a few cytogenetic studies of ICC have been published. Recently, technique of degenerate oligonucleotide primed (DOP)-PCR comparative genomic hybridization (CGH) permits genetic imbalances screening of the entire genome using only small amounts of tumor DNA. In this study chromosomal aberrations in 33 Korean ICC were investigated by DOP-PCR CGH. The common sites of copy number increases were 20q (67%), 17 (61%), 11q11-q13 (42%), 8p12- qter (39%), 18p (39%), 15q22-qter (36%), 16p (36%), 6p21 (30%), 3q25-qter (27%), 1q41-qter (24%), and 5p14-q11.2 (24%). DNA amplification was identified in 16 carcinomas (48%). The frequent sites of amplification were 20q, 17p, 17q23-qter, and 7p. The most frequent sites of copy number decreases were 1p32-pter (21%) and 4q (21%). The recurrent chromosomal aberrations identified in this study provide candidate regions involved in the tumorigenesis and progression of ICC.     

Recurrent chromosomal abnormalities in hepatocellular carcinoma detected by comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to evaluate and map genomic aberrations in 50 hepatocellular carcinomas (HCCs) from patients chronically infected with hepatitis B virus (HBV). CGH clearly detected nonrandom genomic imbalances. Losses were most prevalent on chromosome regions 4q (70%), 8p (65%), 16q (54%), 17p (51%), 13q and 6q (37% each), and 1p (30%). The most frequent gains occurred on 8q (60%), 1q (58%), and 6p and 17q (33% each). In a few cases, sequence amplifications were detected that were mapped to bands 11q12, 12p11, 14q12, and 19q13.1. This study represents the first analysis of primary liver cancers by CGH, and it confirms the presence of previously known chromosomal aberrations in HCC and highlights new quantitative abnormalities and sequence amplifications. These findings should lead to the characterization of new loci involved in liver cancer pathogenesis. Genes Chromosom. Cancer 18:59–65, 1997. © 1997 Wiley-Liss, Inc.     

Molecular cytogenetic analysis of oral squamous cell carcinomas by comparative genomic hybridization, spectral karyotyping, and fluorescence in situ hybridization

We investigated relationships between DNA copy number aberrations and chromosomal structural rearrangements in 11 different cell lines derived from oral squamous cell carcinoma (OSCC) by comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH). CGH frequently showed recurrent chromosomal gains of 5p, 20q12, 8q23 approximately qter, 20p11 approximately p12, 7p15, 11p13 approximately p14, and 14q21, as well as losses of 4q, 18q, 4p11 approximately p15, 19p13, 8p21 approximately pter, and 16p11 approximately p12. SKY identified the following recurrent chromosomal abnormalities: i(5)(p10), i(5)(q10), i(8)(q10), der(X;1)(q10;p10), der(3;5)(p10;p10), and der(3;18)(q10;p10). In addition, breakpoints detected by SKY were clustered in 11q13 and around centromeric regions, including 5p10/q10, 3p10/q10, 8p10/q10 14q10, 1p10/1q10, and 16p10/16q10. Cell lines with i(5)(p10) and i(8)(q10) showed gains of the entire chromosome arms of 5p and 8q by CGH. Moreover, breakages near the centromeres of chromosomes 5 and 8 may be associated with 5p gain, 8q gain, and 8p loss in OSCC. FISH with a DNA probe from a BAC clone mapping to 5p15 showed a significant correlation between the average numbers of i(5)(p10) and 5p15 (R(2) = 0.8693, P< 0.01) in these cell lines, indicating that DNA copy number of 5p depends upon isochromosome formation in OSCC.     

Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations.

Esophageal cancer is the third most prevalent gastrointestinal malignancy in the world. The tumor responds poorly to various therapeutic regimens and the genetic events underlying esophageal carcinogenesis are not well understood. To identify overall chromosomal aberrations in esophageal squamous cell carcinoma, we performed comparative genomic hybridization (CGH). All 17 tumor samples were found to exhibit multiple gains and losses involving different chromosomal regions. The frequency of chromosomal loss associated with this type of tumor was as follows: in 2q (100%), 3p (100%), 13q (100%), Xq (94%), 4 (82%), 5q (82%), 18q (76%), 9p (76%), 6q (70%), 12q (70%), 14q (65%), 11q (59%), and 1p (53%). Interstitial deletions on 1p, 3p, 5q, 6q, 11q, and 12q were detected also. Chromosomal gains were displayed by chromosomes and chromosome areas: 19 (100%), 20q (94%), 22 (94%), 16p (65%), 17 (59%), 12q (59%), 8q (53%), 9q (53%), and 3q (50%). Two sites showing apparent amplification were 11q (70%) and 5p15 (47%). To validate the CGH data, we isolated a BAC clone mapping to 18q12.1. This clone was used as a probe in interphase fluorescence in situ hybridization of tumor touch preparations and allelic loss was clearly revealed. This study represents the first whole-genome analysis in esophageal squamous cell carcinoma for associated chromosomal aberrations that may be involved in either the genesis or progression of this malignancy.     

Frequent gain of copy number on the long arm of chromosome 3 in human cervical adenocarcinoma.

We analyzed genomic aberrations in 20 cervical adenocarcinomas by comparative genomic hybridization (CGH). Most tissue samples (85%) showed DNA copy number changes; gains were more common than losses. The most consistent region of chromosomal gain was mapped to chromosome arm 3q, found in 70% of the cases, with a minimal common region of 3q28-ter. Other recurrent amplifications of genetic material were detected on 17q (45%), 1p (30%), 1q (25%), and 11q (20%). High-level copy number increases were found in chromosomal regions 3q27-ter and 9pter-13. DNA losses were seldom observed, occurring primarily in underrepresented regions of chromosome arms 4q, 13q, and 18q. The presence of high-risk human papilloma virus genomes in the cervical adenocarcinoma samples was detected in 90% of the cases. However, there was no correlation between human papilloma virus type and the pattern of genomic changes. This study is the first report of CGH analysis in human cervical adenocarcinoma. Among the major genomic alterations, our results demonstrate the importance of DNA copy increases of chromosome arm 3q in the development of cervical adenocarcinoma and identify other amplified chromosomal regions that are also associated with cervical carcinogenesis.     

Identification of frequent chromosomal aberrations in ductal adenocarcinoma of the pancreas by comparative genomic hybridization (CGH)

Despite the continuous progress in molecular methodology, the genetic events involved in the initiation and progression of ductal adenocarcinoma of the pancreas remain largely unknown. In this study, 33 pancreatic ductal adenocarcinomas were screened for genomic alterations by comparative genomic hybridization (CGH). To date, most CGH studies of pancreatic cancer have been based on cell lines. To emphasize genetic imbalances that are involved in the in vivo development and progression of pancreatic carcinoma only fresh-frozen or paraffin-embedded tumour samples were analysed in the present study. Twenty-two tumours (67%) showed genomic alterations involving up to three (12%) or more (55%) chromosomal regions. The number and nature of the genetic imbalances did not, however, correlate with tumour stage or grade. Chromosome 18 was preferentially altered in the tumours analysed. Frequent chromosomal losses were found at 18q, 10q, 8p, and 13q. Commonly gained regions were located on 8q and 3q. Moreover, high copy number amplifications of the chromosomal regions 5p, 8q22-ter, 12p12-cen, 19q12-13.2, and 20q were identified. These data provide evidence for the occurrence of characteristic genomic alterations which are of biological relevance for the genesis of pancreatic cancer. The identified altered chromosomal regions may harbour tumour genes which involved in the multistep process of pancreatic carcinogenesis.     

Chromosomal aberrations in nasopharyngeal carcinoma analyzed by comparative genomic hybridization.

To investigate the genomic imbalances associated with nasopharyngeal carcinoma (NPC), we have performed chromosome analysis by comparative genomic hybridization (CGH) on 51 tumors, including 25 primary and 26 recurrent tumors. The most common copy number increases occurred on chromosome arms 12p (59%), 1q (47%), 17q (47%), 11q (41%), and 12q (35%). The minimal overlapping regions were at 12p12-13, 1q21-22, 17q21, 17q25, 11q13, and 12q13. The most frequent losses were from chromosome arms 3p (53%), 9p (41%), 13q (41%), 14q (35%), and 11q (29%). The minimal overlapping regions were at 3p12-14, 3p25-26, 9p21-23, 13q21-32, 14q12-21, and 11q14-23. Compared with the primary cancers, no additional chromosomal change was found in the recurrent tumors; however, the most frequent gain in the recurrent NPCs was at 11q13 (53%) instead of 12p in the primary tumors. An increase of gene alterations correlated with clinical stage. Our results provide a first comprehensive view of the genomic changes associated with NPC and reveal several new sites of genomic imbalance, indicating the possible involvement of novel oncogenes/tumor suppressor genes in the carcinogenesis of NPC.     

Human hepatocellular carcinoma is characterized by a highly consistent pattern of genomic imbalances, including frequent loss of 16q23.1-24.1

Comparative genomic hybridization (CGH) analysis was used to identify chromosomal imbalances in 52 human primary hepatocellular carcinomas (HCCs). The most prominent changes were gains of part or all of chromosome arms 8q (83% of cases) and 1q (73%) and loss of 16q (63%). Other commonly overrepresented sites were 5p, 7q, and Xq. Recurrent sites of DNA sequence amplification included 8q23--24 (five cases) and 11q13--14 (four cases). Other frequently underrepresented sites were 4q, 8p, 16p, and 17p. Taken collectively, these findings and data from other CGH studies of HCCs define a subset of chromosome segments that are consistently over- or underrepresented and highlight sites of putative oncogenes and tumor suppressor genes, respectively, involved in hepatocellular oncogenesis. Loss of heterozygosity analysis with a panel of polymorphic microsatellite markers distributed along 16q defined a minimal region of chromosomal loss at 16q23.1--24.1, suggesting that this region harbors a tumor suppressor gene whose loss/inactivation may contribute to the pathogenesis of many HCCs.     

A combination of molecular cytogenetic analyses reveals complex genetic alterations in conventional renal cell carcinoma

Here we report the complex pattern of genomic imbalances and rearrangements in a panel of 19 renal cell carcinoma cell lines detected with molecular cytogenetic analysis. Consistent heterogeneity in chromosome number was found, and most cell lines showed a near-triploid chromosome complement. Several cell lines showed deletions of the TP53 (alias p53), CDKN2A (alias p16), and VHL genes. Multiplex fluorescence in situ hybridization (M-FISH) analysis revealed chromosome 3 translocated to several other partners chromosomes, as well as breakage events commonly affecting chromosomes 1, 5, 8, 10, and 17. The most common abnormality detected with comparative genomic hybridization (CGH) was deletions of chromosome 3p, with loss of the RASSF1, FHIT, and p44S10 loci frequently involved. CGH gain of 5q showed overrepresentation of the EGR1 and CSF1R genes. Recurrent alterations to chromosome 7 included rearrangement of 7q11 and gains of the EGFR, TIF1, and RFC2 genes. Several lines exhibited rearrangement of 12q11 approximately q14 and overrepresentation of CDK4 and SAS loci. M-FISH revealed several other recurrent translocations, and CGH findings included loss of 9p, 14q, and 18q and gain of 8q, 12, and 20. Further genomic microarray changes included loss of MTAP, IGH@, HTR1B, and SMAD4 (previously MADH4) and gains of MYC and TOP1. An excellent correlation was observed between the genomic array and FISH data, demonstrating that this technique is effective and accurate. The aberrations detected here may reflect important pathways in renal cancer pathogenesis.     

Chromosomal regions involved in the pathogenesis of osteosarcomas

The comparative genomic hybridization technique (CGH) was used to identify common chromosomal imbalances in osteosarcomas (OS), which frequently display complex karyotypic changes. We analyzed 13 high-grade primary tumors, 5 corresponding cell lines, 2 primary tumors grade 2, and 1 recurrent tumor from a total of 16 patients. Some of the CGH results have been verified by fluorescence in situ hybridization (FISH) studies. Gains of chromosomal material were more frequent than losses. Most common gains were observed at 8q (11 cases), 4q (9 cases), 7q (8 cases), 5p (7 cases), and 1p (8 cases). The smallest regions of overlap have been narrowed down to 8q23 (10 cases), 4q12-13 (8 cases), 5p13-14 (7 cases), 7q31-32 (7 cases), 8q21 (7 cases), and 4q28-31 (5 cases). These data demonstrate that a number of chromosomal regions and even two distinct loci on 4q and 8q are involved in the pathogenesis of OS, with gain of 4q12-13 chromosomal material representing a newly identified locus. Seven of 16 cases displayed, besides gain of 8q23 sequences, gain of MYC copies in CGH and FISH. Previous CGH reports confined gain of 8q material to 8cen-q13, 8q21.3-8q22, and 8q23-qter, whereas our data suggest that the loci 8q21 and 8q23-24 are affected in the development of OS. In contrast to recent reports, copy number increases at 8q and 1q21 did not have an unfavorable impact on prognosis in the present series. Genes Chromosomes Cancer 28:329-336, 2000.     

Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization

Acute megakaryocytic leukemia is a rare subtype of AML that is often difficult to diagnose; it is most commonly associated with Down syndrome in children. To identify chromosomal imbalances and rearrangements associated with acute megakaryocytic leukemia, we used G-banding, comparative genomic hybridization (CGH), and whole chromosome painting (WCP) on a variety of primary patients' samples and leukemia cell lines. The most common abnormality was gain of chromosome 19 or arm 19q, which was detected by CGH in four of 12 (33.3%) primary samples and nine of 11 (81.8%) cell lines. In none of the primary samples was this abnormality detected by G-banding analysis. WCP was used to define further the nature of the chromosome 19 gain in the cell lines, which was found to be due to the presence of additional 19q material on marker chromosomes or to cryptic translocations involving 19q. The most common chromosomal loss--detected only in the cell lines--was deletion of chromosomal band 13q14, which was seen in six of 11 (54.5%) cell lines. Other recurrent changes included gains of 1p, 6p, 8q, 11q, 15q, 17q, and 21q and losses of 2, 4q, 5q, 7q, 9p, and 11p. Combining conventional and molecular cytogenetic analyses defined recurrent clonal chromosomal abnormalities, which will aid in the identification of critical genes that are abnormal in acute megakaryocytic leukemia cells.     

Frequent amplification and rearrangement of chromosomal bands 6p12-p21 and 17p11.2 in osteosarcoma

Osteosarcoma (OS) is a highly malignant bone neoplasm of children and young adults. It is characterized by chaotic karyotypes with complex marker chromosomes. We applied a combination of molecular cytogenetic techniques including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) to decipher the chromosomal complexity in a panel of 25 tumors. Combined SKY and G-banding analysis identified several novel recurrent breakpoint clusters and 9 nonrecurrent reciprocal translocations. CGH identified several recurrent chromosomal losses including 2q, 3p, 9, 10p, 12q, 13q, 14q, 15q, 16, 17p, and 18q, gains including Xp, Xq, 5q, 6p, 8q, 17p, and 20q, and high-level chromosomal amplifications at Xp11.2, 1q21-q22, 4p11, 4q12, 5p15, 6p12.1, 8q13, 8q23, 10q11, 10q22, 11q13, 11q23, 12q13-q14, 13q21-q34, 16q22, 17p11.2, 17q21-q22, 18q22, 20p11.2, and 20q12. Frequent amplification and rearrangement involving chromosomal bands at 6p12-p21 and 17p11.2 were found in 28% and 32% of cases, respectively. In an attempt to identify the genes involved in these amplicons, we used three nonoverlapping BAC clones contained within each amplicon as probes for FISH analysis, leading to a more detailed characterization and quantification of the 6p and 17p amplicons.     

Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications

Distinction of adrenocortical carcinoma from benign adrenocortical lesions by standard criteria is often difficult. In order to search for additional diagnostic parameters, a series of 25 adrenocortical tumors, 8 adenomas, 14 primary carcinomas, 1 metastasis, and the 2 adrenocortical carcinoma cell lines SW13 and NCI-H295 were analyzed by the approach of comparative genomic hybridization (CGH). Except for the two smallest adenomas, all tumors showed chromosomal imbalances with a high incidence of chromosomal gains, most frequently involving chromosomes or chromosome arms 5, 7, 8, 9q, 11q, 12q, 14q, 16, 17q, 19, 20, and 22q. The only significant loss of material concerned the distal part of 9p. Furthermore, 21 high-level amplifications were identified in 15 different regions of the genome. The consensus regions of recurrent gains and the focal high-level amplifications allowed identification of a series of chromosomal subregions containing candidate proto-oncogenes of potential pathogenic function in adrenocortical tumors: 1p34.3-pter, 1q22-q25, 3p24-pter, 3q29, 7p11.2-p14, 9q34, 11q12-11q13, 12q13, 12q24.3, 13q34, 14q11.2-q12, 14q32, 16p, 17q24-q25, 19p13.3, 19q13.4, and 22q11.2-q12. A subset of the CGH data was independently confirmed by interphase cytogenetics. Interestingly, the adenomas larger than 4 cm contained gained material of regions also overrepresented in carcinomas. In addition, several chromosomal gains, in particular the high-level amplifications, were exclusive for the malignant status of the tumors. These data indicate that the larger adrenal lesions need to be carefully considered in the diagnosis of adrenocortical tumors, and that genetic aberrations might provide useful markers for a better diagnostic differentiation.     

Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization

Comparative genomic hybridization (CGH) has been applied to detect recurrent chromosome alterations in 62 primary gastric carcinomas. Several nonrandom chromosomal changes, including gains of 8q (31 cases, 50%), 20q (29 cases, 47%) with a minimum gain region at 20q11. 2-q12, 13q (21 cases, 34%) with a minimum gain region at 13q22, and 3q (19 cases, 31%) were commonly observed. The regions most frequently lost included: 19p (23 cases, 37%), 17p (21 cases, 33%), and 1p (14 cases, 23%). High copy number gain (DNA sequence amplification) was detected in 6 cases. Amplification of 8q23-q24.2 and 20q11.2-q12 were observed in 3 cases. Gain of 20q and loss of 19p were confirmed by fluorescence in situ hybridization using corresponding bacterial artificial chromosomes (BAC) clones from those regions. The gain and loss of chromosomal regions identified in this study provide candidate regions involved in gastric tumorigenesis.     

Chromosomal alterations in Malaysian patients with nasopharyngeal carcinoma analyzed by comparative genomic hybridization

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, mainly occurring among the Chinese population. To detect common genetic alterations in NPC, we screened seven cases of NPC using the comparative genomic hybridization (CGH) technique. Before proceeding to the CGH technique, the tumors were first confirmed to consist of 75% tumor cells or more. In brief, the technique consists of binding tumor DNA with normal DNA and human Cot-1 DNA, which is then hybridized to normal metaphase spreads. The slides were then counterstained with 4,6 diamino-2-phenylindole (DAPI II) for detection. Analyses were performed using CGH software (Cytovision). We found genetic alterations in all seven NPC samples. The common chromosomal gains (57%, four cases) were found on chromosome arms 1q, 4p, 5, 7q, 11, 14p, 15q, 18p, and 21p, and common chromosomal losses (43%, three cases) were found on chromosome arm 16p. Our results showed chromosomal alterations in all seven NPC cases in the Malaysian population. This result provides the platform for further investigations to locate tumor suppressor genes and oncogenes at specific chromosomal regions in Malaysian NPC patients.