Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa

AIMS: To investigate the incidence of genetic aberrations in the DNA repair genes in a cohort of oesophageal cancers. METHODS: One hundred oesophagectomy samples of squamous cell carcinoma were studied. Normal and tumour DNA were isolated using a standard phenol/chloroform extraction procedure. Six recommended microsatellite loci with high informativity were analysed. The following markers were used: D2S123 (2p), D3S659 (3p), D3S1255 (3p), Bat 25 (4q), Bat 26 (2p), and Bat 40 (1p). The results were analysed using software attached to an automated DNA sequencer. The molecular data were then correlated with clinicopathological parameters. RESULTS: The incidence of microsatellite instability and loss of heterozygosity was very low. There was no significant correlation between the clinicopathological and molecular data. However, D2S123 genetic abnormalities were seen more frequently in both moderately and well differentiated tumours than in poorly differentiated tumours (p = 0.033). Follow up data were available for only 67 of the 100 patients. Fifty patients were alive and 17 patients had died. CONCLUSION: Low frequencies of genetic aberrations in these mismatch repair loci are found in squamous carcinomas of the oesophagus from a high incidence area in South Africa.     

Genetic characterisation of invasive breast cancer: a comparison of CGH and PCR based multiplex microsatellite analysis

AIMS: Comparative genomic hybridisation (CGH) is a reliable tool to gain an overview of all unbalanced chromosomal alterations within a tumour. Nevertheless, the high numbers of tumour cells required and the comparatively low resolution are drawbacks of this technique. Polymerase chain reaction (PCR) based multiplex microsatellite analysis represents a semi-automated, highly reproducible method, which requires small amounts of tumour cells. This is a comparative study of CGH and microsatellite analysis. METHODS: Eighty one samples of invasive breast cancer were investigated by two sensitive multiplex PCRs containing three microsatellites each of six markers (D6S261, D11S907, D6S300, D11S927, D8S272, and D11S925), and two additional microsatellite markers located within intron 1 of the epidermal growth factor receptor gene (egfr) and p53 (p53CA). RESULTS: At least one example of loss of heterozygosity was detectable in all breast cancer tissues. However, the overall rate of accordance between the two methods tested was only 61%. An increasing rate of the number of genetic alterations in each case was mirrored by a constantly increasing fractional allelic loss index. CONCLUSIONS: PCR based multiplex microsatellite analysis using this panel of eight microsatellite markers not only enables the characterisation of cells that have malignant potential in a high frequency of patients with breast cancer, but can also give an estimate of the degree of genetic progression.     

Conserved genetic findings in metastatic bladder cancer: a possible utility of allelic loss of chromosomes 9p21 and 17p13 in diagnosis

CONTEXT: Molecular analysis of microsatellite alterations of biologically distinct tumor cell subpopulations from the same patient may aid in the determination of tumor origin and further our understanding of the genetic basis of cancer progression. DESIGN: The authors examined the pattern of allelic loss with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymph node metastases at the time of surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method. RESULTS: The overall frequency of allelic loss was 78% in primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% with TP53. The frequency of allelic loss in matched metastatic cancer was 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the primary cancer. CONCLUSIONS: The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer was conserved in paired metastatic carcinoma. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.     

High-resolution deletion mapping of chromosome 14 in stromal tumors of the gastrointestinal tract suggests two distinct tumor suppressor loci

DNA copy number losses at chromosome arm 14q are the most frequently occurring aberrations in gastrointestinal stromal tumors (GISTs). To characterize the deletion at 14q, we performed comparative genomic hybridization (CGH) and high-resolution deletion mapping using a panel of 32 polymorphic microsatellite markers in 30 GISTs. The GISTs were classified according to their metastatic potential and mitotic counts into 15 low-risk and 15 high-risk tumors. Losses with a minimal common overlapping region at 14q12-q24 were detected by CGH in 16 tumors (53) (nine low-risk and seven high-risk). Investigation with microsatellite markers was informative in 690 analyses (72%). Loss of heterozygosity (LOH) with at least one marker was detected in 279 analyses in 24 tumors (80%). Deletions were equally frequent in low-risk and high-risk GISTs. Two common deletion regions were identified at 14q11.1-q12 and 14q23-q24.3. The highest frequencies of deletions were seen in regions corresponding to markers D14S283 (20/28, 71%) at 14q11.1-q12 and D14S258 (17/27, 63%) at 14q23-q24, suggesting that these are two tumor suppressor loci.     

Genetic heterogeneity by comparative genomic hybridization in BRCAx breast cancers

The chromosomal changes in eight familial BRCAx breast cancers (i.e., negative for BRCA1 or BRCA2) were analyzed by comparative genomic hybridization (CGH) to investigate intratumor heterogeneity. This was the first step in a study of most frequent chromosomal aberrations in BRCAx familial breast cancers. Laser microdissection analysis of paraffin tissue samples was followed by whole-genome amplification. CGH was performed on DNA isolated from two to three different cell groups per case to detect any cytogenetic aberrations in important clones that might have been missed when analyzing DNA extracted from large numbers of cells. The results were compared, to evaluate the influence of tumor heterogeneity on CGH, and the heterogeneity was confirmed comparing CGH with fluorescence in situ hybridization results. Different chromosomal aberrations were detected between adjacent clones within the same section, which highlights the utility of microdissection in addressing the problem of heterogeneity in whole-genome studies. Some chromosomal regions were more frequently altered in the eight BRCAx tumors; loss of 2q, 3p, 3q, 8p, 9p, and 15q and gains of 1p, 4p, 4q, 5p, 6q, 12q, and 19p were the most common. Further studies focusing on specific genes and sequences with more sensitive approaches, such as array-CGH, are warranted to confirm these findings.     

Accuracy of an array comparative genomic hybridization (CGH) technique in detecting DNA copy number aberrations: comparison with conventional CGH and loss of heterozygosity analysis in prostate cancer

Although genomic DNA microarray (array comparative genomic hybridization [CGH]) technique is a rapid and powerful diagnostic tool for the comprehensive analysis of detailed chromosomal alterations of DNA copy numbers, its accuracy has not been well demonstrated. To clarify the accuracy of this technique, we applied array CGH spotted with 283 specific genes to 11 clinical prostate cancers, and the results were compared with comparative genomic hybridization (conventional CGH) and loss of heterozygosity (LOH) analysis using microsatellite DNA markers. The overall rate of correspondence between array CGH and conventional CGH with respect to the loss of DNA sequences was 94.5%. When the results of both CGH techniques were compared with those of LOH analysis, the correspondence rate of array CGH was significantly higher than that of conventional CGH (93.4% vs. 72.2%, P<0.05). In conclusion, the accuracy of array CGH was higher than that of conventional CGH in detecting losses of the DNA sequences. Array CGH is shown to be a promising tool for screening to identify unknown genes involved in tumorigenesis in prostate cancer.     

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer.

Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P=0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P=0.04 by log-rank test) and disease progression (P=0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.     

Gastric cancers in young and elderly patients show different genomic profiles

Although most gastric cancers occur in elderly patients, a substantial number of cases of this common disease occur in young patients. Gastric cancer is a heterogeneous disease at the genomic level and different patterns of DNA copy number alterations are associated with different clinical behaviour. The aim of the present study was to explore differences in DNA copy number alterations in relation to age of onset of gastric cancer. DNA isolated from 46 paraffin-embedded gastric cancer tissue samples from 17 patients less than 50 years of age [median 43 (21-49) years] and 29 patients greater than or equal to 70 years of age [median 75 (70-83) years] was analysed by genome-wide microarray comparative genomic hybridization (array CGH) using an array of 5000 BAC clones. Patterns of DNA copy number aberrations were analysed by hierarchical cluster analysis of the mode-normalized and smoothed log(2) ratios of tumour to normal reference fluorescence signal intensities using TMEV software, after which cluster membership was correlated with age group. In addition, supervised analysis was performed using CGH Multi-array. Hierarchical cluster analysis of the array CGH data revealed three clusters with different genomic profiles that correlated significantly with age (p = 0.006). Cluster 1 mainly contained young patients, while elderly patients were divided over clusters 2 and 3. Chromosome regions 11q23.3 and 19p13.3 contributed most to age-related differences in tumour profiles. Gastric cancers of young and old patients belong to groups with different genomic profiles, which likely reflect different pathogenic mechanisms of the disease.     

Evaluation of adult papillary thyroid carcinomas by comparative genomic hybridization and microsatellite instability analysis

To clarify the mechanism of tumorigenesis in papillary thyroid carcinoma (PTC) and ascertain whether genomic changes correlate with histologic features, we conducted a comprehensive molecular evaluation of PTC using comparative genomic hybridization (CGH) and microsatellite instability (MSI) analysis in a set of 17 histologically well-characterized PTC specimens. To our knowledge, this is the first study that evaluates chromosomal and nucleotide instability in the same PTC tumor specimens. Four of 15 samples (27%) had aberrations detected by CGH. All four had a partial or complete gain of chromosome 20, and 3 of 4 had a partial or complete loss of chromosome 13. No MSI was detected in any of the PTC samples (n=16), and all samples examined by immunohistochemistry (n=9) expressed the DNA repair enzymes hmlh1 and hmsh2. All PTC samples with abnormal CGH had vascular invasion or invasion of the thyroid capsule, and there was a significant correlation between the presence of chromosomal aberrations and capsular/vascular invasion (P=0.026). We conclude that although chromosomal and microsatellite instability are uncommon in PTC, tumors with chromosomal aberrations are more likely to be associated with invasion.     

Association between genomic alterations and metastatic behavior of colorectal cancer identified by array‐based comparative genomic hybridization

Colorectal cancers (CRCs) exhibit multiple genetic alterations, including allelic imbalances (copy number alterations, CNAs) at various chromosomal loci. In addition to genetic aberrations, DNA methylation also plays important roles in the development of CRC. To better understand the clinical relevance of these genetic and epigenetic abnormalities in CRC, we performed an integrative analysis of copy number changes on a genome‐wide scale and assessed mutations of TP53, KRAS, BRAF, and PIK3CA and DNA methylation of six marker genes in single glands isolated from 39 primary tumors. Array‐based comparative genomic hybridization (array‐CGH) analysis revealed that genomic losses commonly occurred at 3q26.1, 4q13.2, 6q21.32, 7q34, 8p12‐23.3, 15qcen and 18, while gains were commonly found at 1q21.3‐23.1, 7p22.3‐q34, 13q12.11‐14.11, and 20. The total numbers and lengths of the CNAs were significantly associated with the aberrant DNA methylation and Dukes' stages. Moreover, hierarchical clustering analysis of the array‐CGH data suggested that tumors could be categorized into four subgroups. Tumors with frequent DNA methylation were most strongly enriched in subgroups with infrequent CNAs. Importantly, Dukes' D tumors were enriched in the subgroup showing the greatest genomic losses, whereas Dukes' C tumors were enriched in the subgroup with the greatest genomic gains. Our data suggest an inverse relationship between chromosomal instability and aberrant methylation and a positive association between genomic losses and distant metastasis and between genomic gains and lymph node metastasis in CRC. Therefore, DNA copy number profiles may be predictive of the metastatic behavior of CRCs. © 2012 Wiley Periodicals, Inc.     

Characterizing genetically stable and unstable gastric cancers by microsatellites and array comparative genomic hybridization

Gastric cancer (GCA) displays a variety of genomic aberrations, including DNA copy number alterations, microsatellite instability (MSI), and loss of heterozygosity (LOH). The main aim of the present work was to determine the copy number aberrations in tumors with and without MSI or LOH. Fifteen fresh-frozen GCA samples, 11 of the intestinal and 4 of the diffuse type, were grouped by microsatellite analysis into high-level MSI (MSI-H, n = 2), LOH (n = 5), and microsatellite stable, LOH not detected (MSS/LOH-N, n = 8) tumors. The DNA samples were subsequently analyzed by array comparative genomic hybridization with 16,000 cDNA clones. As expected, the LOH tumors showed more copy number changes; however, the frequency of small-size amplifications was similar across all tumor groups. In addition, the cDNA arrays detected two apparently single-gene amplicons, at 11q13 (CCND1) and 12p12.1 (K-RAS), the presence of which were confirmed using oligonucleotide arrays. A novel amplicon at 5q13.2 was found only in diffuse-type tumors, which were otherwise genetically stable. The results suggest that DNA copy number changes may also occur in gastric cancers that show genomic stability in microsatellite analysis.     

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.     

Loss of heterozygosity on chromosome arm 3p in nasopharyngeal carcinoma

We have examined 17 primary undifferentiated nasopharyngeal carcinoma biopsies for allelic loss on 3p, comparing the findings in tumors with those in normal lymphocyte DNA from the same patients. Ten polymorphic microsatellite markers were used between 3p13 and 3p26. Allelic loss was observed in 12 samples (70%). Two loci were most frequently affected: D3S1067 (3p21.1-14.3) in 60% and D3S1217 (3p14.2-14.1) in 58%. One tumor seemed to have a homozygous deletion at 3p26, detected by the D3S1297 marker. Analysis of the clinical data showed that an increased number of aberrations in 3p was correlated with more advanced tumor stages. Genes Chromosom Cancer 17:118–126 (1996). © 1996 Wiley-Liss, Inc.     

Microsatellite alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma

A series of 20 hepatocellular carcinomas and 8 intrahepatic cholangiocarcinomas was screened from the Korean population for microsatellite alterations, including a loss of heterozygosity and replication errors using nine microsatellite markers containing several genes. The microsatellite results and our previous comparative genomic hybridization results of two tumors were compared at each locus, and the correlations between these and clinicopathologic variables were examined. The most characteristic findings were found at 13q. Replication errors were prevalent at D13S160 (13q21.2 approximately q31) and D13S292(13q12). The incidence of loss of heterozygosity, however, was higher at D13S153 (13q14.1 approximately q14.3) and D13S265(13q31 approximately q32). In contrast, there were higher deletion frequencies observed in hepatocellular carcinoma (HCC) and higher amplification frequencies observed in intrahepatic cholangiocarcinoma at 13q in our previous comparative genomic hybridization (CGH) study. Higher frequencies of replication errors were observed at D16S408 (13q12 approximately q21) and D16S504(13q23 approximately q24) in the HCC. This study found that significant differences in the patterns of genetic instability of microsatellites were dependent on the chromosomal loci. It is believed that certain genes at altered CGH regions, which are relevant to the development and/or progression of these cancers, are activated by different mutation mechanisms.     

软组织肿瘤的比较基因组杂交研究进展

比较基因组杂交(comparative genomic hybridization,CGH) 是1992年建立起来的重大分子细胞遗传学分析技术,它在对整个基因组DNA拷贝数变异的检测方面是一种有效的方法。通过CGH检测,可找出染色体DNA拷贝数的变异特点,即基因拷贝数的扩增或丢失,从而确定相关的癌基因和抑癌基因所在的区域,为探讨肿瘤的发病机制提供依据。在过去的十几年中,用CGH对各种软组织肿瘤进行研究,已探测到了各种各样的有不同程度特异性的基因组的不平衡性,不仅开辟了探测各种癌症相关基因的新途径,并且找到了一些与临床相关的基因改变,可用于肿瘤的发生、发展、鉴别诊断、预后以及治疗等研究。     

Amplification of 3q26 approximately qter correlates with tumor progression in head and neck squamous cell carcinomas

Biological characteristics of malignant tumors including head and neck squamous cell carcinoma (HNSCC) are greatly affected by genetic alterations. However, the relationship between chromosomal aberrations and pathologic tumor stage in HNSCC has not been elucidated. In 32 patients, DNA sequence copy number aberrations (DSCNA) were surveyed by comparative genomic hybridization (CGH) combined with a microdissection method. The average number of DSCNA was 15.3 per tumor and increased with tumor stage (P<.05). DNA copy number gain was detected at 3q26 approximately qter in 29 tumors (91%), and 13 of these tumors displayed marked DNA amplification. Tumor stage was linked with this amplification (P<.05). The increase in DSCNA and amplification of 3q26 approximately qter are likely to be useful markers for estimating tumor progression in HNSCC.     

Comparative genomic hybridization and amplotyping by arbitrarily primed PCR in stage A B-CLL.

Cytogenetic analysis is useful in the diagnosis and to assess prognosis of B-cell chronic lymphocytic leukemia (B-CLL). However, successful cytogenetics by standard techniques has been hindered by the low in vitro mitotic activity of the malignant B-cell population. Fluorescence in situ hybridization (FISH) has become a useful tool, but it does not provide an overall view of the aberrations. To overcome this hurdle, two DNA-based techniques have been tested in the present study: comparative genomic hybridization (CGH) and amplotyping by arbitrarily primed PCR (AP-PCR). Comparative genomic hybridization resolution depends upon the 400-bands of the human standard karyotype. AP-PCR allows detection of allelic losses and gains in tumor cells by PCR fingerprinting, thus its resolution is at the molecular level. Both techniques were performed in 23 patients with stage A B-CLL at diagnosis. The results were compared with FISH. The sensitivity of AP-PCR was greater than CGH (62% vs. 43%). The use of CGH combined with AP-PCR allowed to detect genetic abnormalities in 79% (15/19) of patients in whom G-banding was not informative, providing a global view of the aberrations in a sole experiment. This study shows that combining these two methods with FISH, makes possible a more precise genetic characterization of patients with B-CLL.     

Deletions of 9p21 and TP53 in bladder cancer.

The objective of this study was to characterize the alterations of 9p21 and TP53 in Korean transitional bladder cancer and to assess the relationship between the histopathologic parameter and the alteration of these genes. Allele loss in 29 surgically resected transitional cell carcinoma was examined by using the multiplex PCR with 7 and 1 microsatellite markers for 9p21 and TP53, respectively. Twenty-one (72%) demonstrated allele loss at 9p21 and/or TP53. Deletion at the 9p21 region was detected in 17(61%) of 28 informative cases at one or more loci, and LOH at TP53 was found in 12(55%) of 22 informative cases. Of 7 microsatellite markers for 9p21, allele loss occurred the most frequently at locus D9S162(69%) and D9S104(69%). Additionally, hemizygous deletion was slightly more common than homozygous deletion. Deletion at 9p21 and TP53 was not related with increased grade. These results suggest that the alteration of 9p21 may be an early event in the development of Korean bladder cancer, while p53 gene may be involved in early event of some bladder cancers as well as in their late events.     

Resolution of genotypic heterogeneity in prostate tumors using polymerase chain reaction and comparative genomic hybridization on microdissected carcinoma and prostatic intraepithelial neoplasia foci

Prostate cancer (CaP) is a multifocal heterogenous disease. A major challenge in CaP research is to identify genetic biomarkers that herald aggressive transformation. To investigate the effect of tumor heterogeneity on the analysis of genomic aberration, we compared the results of comparative genomic hybridization (CGH) analysis of DNA extracted from tumor bulk against that of DNA amplified by degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) from homogeneous cell population obtained by laser capture microdissection of discrete tumor foci. Sampling by microdissection, aberrations were observed in three of three foci of carcinoma involved with prostatic capsule, and in two of three prostatic intraepithelial neoplasia (PIN) foci examined. Carcinoma foci consistently exhibited more extensive aberrations than the PIN samples obtained from the same tumor. Within these samples, the different tumor foci exhibited gain of 8q, whereas PIN showed no consistent aberration. Using bulk extracted DNA, CGH detected aberrations in only 3 of 21 samples investigated, despite the known trisomy 8 status, as revealed by fluorescence in situ hybridization. The results of this study demonstrate that CGH analysis using bulk dissected fresh tissue is insufficiently sensitive to fully detect the chromosomal numerical aberrations in CaP. Given the considerable intratumor genomic heterogeneity, CGH with microdissection and DOP-PCR amplification provides a more complete repertoire of aberrations as well as a better phenotype-genotype correlation in prostate tumors.     

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.