Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping

The molecular events involved in pancreatic cancer are becoming increasingly well characterized, with mutations in the dominant oncogene KRAS and the tumour suppressor genes TP53, CDKN2A and MADH4 being typically observed. However, other genetic abnormalities remain to be identified and molecular cytogenetics may be useful to detect chromosomal loci involved in recurrent rearrangements. We have used spectral karyotyping to characterize cytogenetic aberrations in a panel of 20 human pancreatic carcinoma cell lines and confirmed their identities by dual and triple color fluorescence in situ hybridization. The most common partial or whole-arm gains involved 5p, 7q, 12p, 1q, 7p, 5q, 9p, 9q and 11p. The most common partial or whole-arm losses affected 9p, 11q, 18q, 3p, 2q and 1p, as well as the short arms of the acrocentric chromosomes. Spectral karyotyping allowed us to identify a number of recurrent structural aberrations, all of them unbalanced: most frequently i(5)(p10), del(11)(q23), i(12)(p10), i(1)(q10), del(7)(q22) and del(10)(p11). Spectral karyotyping mapped the complex aberrations occurring in pancreatic cancer cell lines and identified non-random patterns of chromosomal rearrangement. This comprehensive characterization should be useful to direct future investigation. The observation that loss at 11q and gains at 5p with i(5)(p10) and 12p with i(12)(p10) are more frequent changes than previously reported would justify more intensive investigation of these chromosomal regions.     

Allelotype analysis of the myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorders found predominantly in the elderly. The molecular mechanisms underlying the development of MDS remain obscure. In order to begin to identify tumor suppressor genes involved in these disorders, we performed a detailed microsatellite allelotype of chromosomal deletions associated with MDS. DNAs from both bone marrow and peripheral blood of 32 MDS patients were studied using 84 highly informative microsatellite markers on all autosomal arms, excluding the short arms of the acrocentric chromosomes. A high percentage of loss of heterozygosity (LOH) was identified on chromosome 5q (40% of informative cases), 7q (45%), 17p (23%) and 20q (20%), which corresponds to the most common cytogenetic abnormalities reported in MDS. In addition, a high incidence of LOH (> or =20%) was observed on chromosomal arms which had not been previously reported including 1p (36%), 1q (35%), and 18q (23%). This extensive allelotype analysis focuses attention on several novel genomic regions that probably contain novel tumor suppressor genes whose loss of function contributes to the development of MDS.     

Allelotype analysis of adenocarcinoma of the gastric cardia.

To identify chromosomal loci involved in the development of proximal gastric adenocarcinoma, this study delineated the pattern of allelic imbalance in a series of 38 adenocarcinomas arising in the gastric cardia. A total of 137 microsatellite markers covering all autosomal arms, excluding acrocentric arms, were analysed. A mean of 35 out of a total of 39 chromosomal arms studied were informative for each patient. The tumour group demonstrated a high level of allelic imbalance, with an observed median fractional allelic imbalance of 0.47 for the 29 intestinal-type adenocarcinomas and 0.54 for the nine diffuse-type adenocarcinomas. Allelic imbalance was detected in >50% of informative cases in both histological subtypes on a number of chromosomal arms. In the intestinal subtype, these included, 3p (61%), 4q (71%), 5q (59%), 8p (60%), 9p (65%), 9q (83%), 12q (52%), 13q (52%), 17p (78%) and 18q (70%). A higher incidence of allelic imbalance was detected on chromosome 16q in tumours of the diffuse type relative to those of the intestinal type. A more detailed mapping on chromosomes 4q and 6q identified a number of cases with subchromosomal breakpoints. In conclusion, this analysis has indicated regions of the genome potentially involved in the development of proximal gastric carcinomas.     

Allelic loss in the progression of myelodysplastic syndrome

To elucidate the genetic events that may play an important role in the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML), we performed allelotype analysis of 24 individuals using matched MDS and AML samples from the same patients. Because the evolution can take years to occur, we used DNAs extracted from archival samples. These samples were analyzed with 79 microsatellite markers, which mapped to each of the autosomal arms except the short arms of the acrocentric chromosomes. Loss of heterozygosity on at least one locus was observed in 18 of the 24 cases (75%) as the disease progressed. Frequent allelic loss in >20% of the informative cases was observed on chromosome arms 6q (31%), 7p (23%), 10p (31%), 11q (27%), 14q (25%), and 20q (23%). Although cytogenetic information was available for many of our cases with allelic loss on 6q, 7p, 10p, 11q, 14q, and 20q, no deletions were observed on these arms. Fractional allelic loss, calculated for each sample as the total number of chromosomal arms lost per total number of arms with information, showed a median value of 0.06 and a mean of 0.15 (range, 0-0.59). No microsatellite instability at more than one marker was found in any of the samples. These results suggest that tumor suppressor genes exist on 6q, 7p, 10p, 11q, 14q, and 20q that have an important role in the evolution of MDS to AML when they are mutated.     

Genetic analysis of head and neck squamous cell carcinoma using comparative genomic hybridisation identifies specific aberrations associated with laryngeal origin

Head and neck squamous cell carcinoma (HNSCC) demonstrates significant differences in the biological and clinical behaviour of tumours found at different sub-sites. We investigated the genetic profiles of 68 carcinomas (larynx n=35, hypopharynx n=19, oropharynx n=14) using chromosomal comparative genomic hybridisation in order to identify sub-site specific differences. Multiple genetic aberrations were found throughout the tumour genomes, including +3q (82%), -3p (75%), +8q (66%), +5p (49%), +7q (49%), +1q (47%), -4p (46%), -11q (46%), -13q (46%), -5q (44%), +11q (43%) and +12p (43%). The mean number of chromosomal arms with at least one aberration was 15. Laryngeal carcinomas (LSCC) were found to have significantly more aberrations on chromosomal arms than oropharyngeal carcinomas (OpSCC); (mean of 17 vs. 11, respectively (p=0.011). It was noted that -4p, +8q, +12q, and -18q were significantly associated with LSCC when compared with both hypopharyngeal SCC (HpSCC) and OpSCC. HpSCC was significantly associated with -2q whereas no aberrations were found to be significantly associated with OpSCC. In conclusion a large number of common chromosomal aberrations are associated with HNSCC however in addition further aberrations are significantly associated with individual sub-sites of head and neck cancer. These aberrations may be responsible for the diverse biological behaviour of these different tumour types. Further research is required to identify the specific genes associated with these chromosomal regions and evaluate their individual impact on disease progression.     

Investigations for fine mapping of amplifications in chromosome 3q26.3-28 frequently occurring in squamous cell carcinomas of the head and neck

OBJECTIVE: Overrepresentations of chromosomal material on the long arm of chromosome 3 frequently occur in squamous cell carcinoma of the head and neck. This experimental study was conducted for further fine mapping of these overrepresentations by interphase fluorescence in situ hybridization (FISH) of tumor cells in cell lines. METHODS: Seven cell lines derived from squamous cell carcinomas of the head and neck were investigated by comparative genomic hybridization to analyze unbalanced chromosomal aberrations. Overrepresentations of chromosomal material on the telomeric part of the long arm of chromosome 3 were further analyzed by interphase FISH using YAC contig clones. RESULTS: Chromosomal aberrations which frequently occurred were overrepresentations on 5p (n = 4), 7p (n = 5), 11q13 (n = 3), 15q (n = 5), 17q (n = 3), 19q (n = 2), 20q (n = 2) and 22q (n = 3). Reoccurring losses of chromosomal material were found in 3p (n = 3), 7q (n = 2), 18q (n = 3) and 19p (n = 2). Gains of chromosomal material on chromosome 3q were found in 4 out of 7 cell lines, with a high copy number of amplifications occurring in the chromosomal region of 3q26.3-28. Further experiments revealed a physical mapping of this amplification to a narrow band of 13.8 Mbp on chromosome 3q, whose amplification borders were represented by the YAC clones 754_f_3 centomeric and 955_b_2 telomeric. CONCLUSIONS: By FISH, the amplification of chromosomal material on 3q could be fine mapped on a narrow band on 3q26.3-27. This aberration can be considered as a breakpoint in tumorigenesis. Putative candidate oncogenes and tumor suppressor genes located in this region might be a target for mutations leading to tumor progression.     

Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma.

We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.     

Prognostic value of genomic alterations in head and neck squamous cell carcinoma detected by comparative genomic hybridisation

A total of 45 primary head and neck squamous cell carcinomas were analysed by comparative genomic hybridisation to identify regions of chromosomal deletion and gain. Multiple regions of copy number aberration were identified including gains affecting chromosomes 3q, 8q, 5p, 7q, 12p and 11q and deletion of material from chromosomes 3p, 11q, 4p, 5q, 8p, 10q, 13q and 21. Kaplan-Meier survival analysis revealed significant correlations between gain of 3q25-27 and deletion of 22q with reduced disease-specific survival. In addition, gain of 17q and 20q, deletion of 19p and 22q and amplification of 11q13 were significantly associated with reduced disease-free survival. A Cox proportional hazards regression model identified deletion of 22q as an independent prognostic marker. The data presented here provide further evidence that the creation of a genetically based tumour classification system will soon be possible, complementing current histopathological characterisation.     

Allelotype study of primary hepatocellular carcinoma.

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell to a malignant cell by allowing it to escape from normal control of growth. In order to learn (a) how many tumor suppressor genes are involved in the tumor progression of hepatocellular carcinoma, (b) whether there is any association among allelic losses of chromosomes, or (c) whether integration of hepatitis B virus into host DNA influences any particular chromosomal losses, we have examined loss of heterozygosity with 44 restriction fragment length polymorphism markers in 46 cases of hepatocellular carcinoma. The markers represented all chromosomal arms except 5p, 8p, 9p, 18p, and acrocentric chromosomes. Allelic losses in tumors indicated that five tumor suppressor genes, located on chromosomes 5q, 10q, 11p, 16q, and 17p, may be involved in this cancer. However, no significant associations were observed among the various allelic losses or between the integration of hepatitis B virus and chromosomal losses. Furthermore, a deletion map for chromosome 16q indicated the localization of a tumor suppressor gene between q22 and q24 and that for chromosome 17p suggested the existence of a second tumor suppressor gene in addition to the p53 gene.     

Genotypic analysis of esophageal squamous cell carcinoma by molecular cytogenetics and real-time quantitative polymerase chain reaction

We performed an integrated cytogenetic study using a combination of comparative genomic hybridization (CGH), spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) to analyze chromosomal aberrations associated with 8 human esophageal squamous cell carcinoma (EC-SCC) cell lines, and used real-time quantitative PCR (Q-PCR) to study the copy number changes of two candidate genes of chromosome 3q, PIK3CA and TP63, in 20 primary tumors of EC-SCC. The pooled CGH results revealed frequent gain abnormalities on chromosome arms 1p, 1q, 3q, 5p, 6p, 7p, 7q, 8q, 9q, 11q, 12p, 14q, 15q, 16p, 16q, 17q, 18p, 19q, 20q, 22q, and Xq, while frequent losses were found on 3p, 4, 5q, 6q, 7q, 9p, and 18q. SKY detected 195 translocations, 13 deletions and 2 duplications. Among the 374 breakpoints, most clustered at the centromeric regions, such as 8q10, 13q10, 7q10, 9q10, 14q10, 15q10, 16q10, 21q10, and 22q10, but also at other regions, including 3q (3q21, 3q22, 3q25), 7p (7p22, 7p14, 7p12), 7q (7q21, 7q31, 7q32), 8q (8q21.1, 8q23), 11q (11q21, 11q24), 13q (13q14) and 18q (18q21). There was a good correlation between the number of aberrations identified by CGH and SKY (r=0.667; p=0.035). Combined CGH and SKY analyses indicated that chromosomes 3, 7, 9, 11, 14, 16, 18, 19, 20, and 22 harbored higher frequency of chromosomal aberrations than expected. FISH using BAC clones containing oncogene PIK3CA and TP63 found that both genes were amplified in 6 and 5 cell lines, respectively. Q-PCR analysis of primary tumors revealed amplification of PIK3CA and TP63 in 100% and 80% of the cases. Average copy number of PIK3CA per haploid genome was greater than that of TP63 (6.27 vs 2.73), and the difference showed statistical significance (p<0.001). Combination of CGH, SKY and FISH could reveal detailed chromosomal changes associated with esophageal cancer cells, and Q-PCR could assess the change of the candidate genes in clinical samples in a high throughput way.     

DNA amplification on chromosome 7q in squamous cell carcinoma of the tongue

Squamous cell carcinoma of the head and neck exhibit a highly variable picture of chromosomal aberrations. In the present study the clearly defined anatomical region of the tongue was analyzed for potentially specific patterns of chromosomal alterations. Fresh tumor samples from 18 patients afflicted by squamous cell carcinoma of the tongue constituted the clinical basis of the present investigation. The tumor samples were analyzed on the basis of comparative genomic hybridization (CGH), a molecular cytogenetic FISH-approach. Gains in DNA copy numbers were detected as the predominant imbalance on chromosomes 7q (9/18), 3q (48/18), 16p (7/18) and 20q (7/18). The regions of minimal overlap on these chromosomes were mapped to 7q11.2q11.3 and 3q26. A conspicuous finding was the frequent detection of amplifications in the 7q11 region. Gains in the 7q region have been rarely reported in CGH studies of tumors derived from different regions of the head and neck. Amplifications on 7q could thus be specifically linked with the tongue region and could correlate with specific clinical factors of this tumor entity.     

Comparative genomic hybridization analysis detected frequent overrepresentation of chromosome 3q in squamous cell carcinoma of the lung

The aim of this study was to provide cytogenetic data about squamous cell carcinomas of the lung and to evaluate their characteristic alterations and histogenetic relations. We analyzed 41 squamous cell lung carcinomas by comparative genomic hybridization (CGH) technique. CGH was performed using directly fluorochrome-conjugated DNA. Chromosomal regions where the mean ratio fell below 0.75 were therefore considered to reflect DNA copy number loss (underrepresentation), whereas regions where the mean ratio exceeded 1.25 were considered gains (overrepresentations) in the tumor genome. Overrepresentations were considered to be high-level amplification when the fluorescence ratio exceeded 1.5. Chromosomal imbalances were observed in every case. Copy number gains frequently were detected at 3q, 5p, 8q, 12p, and Xq. Losses were found at 16p, 4q, 5q, 3p, 17p, and 16q. DNA amplifications were observed at 12 regions: 3q26.1-27, 8q13-23.1, 12p12.3-pter, 12q15, 2p14-16, 4q28-31.2, 5p13.1-pter, 6q21-22.3, 7p11.2-13, 13q21.2-32, 18p11.2-pter, and 20p11.2-pter. Gains on 3q were frequently detected not only in the more than 3 cm group (79%) but also in the 3 cm or less group (77%). The mean frequency of gained or lost chromosomal regions was 7.2+/-4.7 in the 3 cm or less group (n=13) and 10.2+/-6.3 in the more than 3 cm group (n=28) (P=0.4503). The mean frequency of gained or lost chromosomal regions was significantly higher in the carcinoma with lymph node metastasis group (12.5+/-7.6 regions) (n=12) than in the carcinoma without lymph node metastasis group (7.9+/-4.6) (n=29) (P=0.0251). In conclusion, an increased copy number at 3q may contribute to the development of squamous cell carcinoma of the lung.     

Common regions of deletion on chromosomes 5q, 6q, and 10q in renal cell carcinoma.

Relatively frequent losses of heterozygosity on chromosomes 5q, 6q, and 10q, in addition to loss of heterozygosity on the short arm of chromosome 3, have been observed in renal cell carcinomas. As the first step toward isolation of tumor suppressor genes on these three chromosomal arms, we used six restriction fragment length polymorphism markers for 5q, nine for 6q, and eight for 10q to identify regions commonly deleted in a panel of 64 renal cell carcinomas. Allelic losses were common at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene was recently identified; at chromosome 6q27; and at chromosome 10q21-23. Furthermore, as association was observed between accumulation of allelic losses on these three chromosomal arms and progression of tumors. Loss of heterozygosity on chromosome 5 showed a correlation with the histopathological grade of a given tumor and the incidence of distant metastasis.     

Glutathione S-transferase pi amplification is associated with cisplatin resistance in head and neck squamous cell carcinoma cell lines and primary tumors

PURPOSE: The purpose is to evaluate the association of glutathione S-transferase pi (GST-pi) amplification and cisplatin resistance in head and neck cancer. EXPERIMENTAL DESIGN: An analysis of chromosomal abnormalities in 10 head and neck cancer cell lines by comparative genomic hybridization was performed. GST-pi amplification and expression were evaluated in head and neck cell lines and paraffin-embedded tissue by fluorescence in situ hybridization (FISH) and immunohistochemistry. RESULTS: Changes in the DNA copy number were seen in all 10 cell lines by comparative genomic hybridization. The most frequent chromosomal alterations were: gain at 3q; loss at 3p; gain at 8q; loss of 18q; gain at 20q; loss at 8p; and gain of 11q11-q13. Using FISH, 9 of 10 cell lines showed increased GST-pi copy number. GST-pi amplification was detected in 7 of 10 cell lines. Five were relatively cisplatin resistant, and 2 were relatively cisplatin sensitive (mean IC(50), 11.2 and 2.75 microM). Two relatively cisplatin-sensitive cell lines showed GST-pi gain and another relatively cisplatin-sensitive cell line had predominantly two copies of the gene. In 10 tumor specimens, 4 had two copies of GST-pi. All 4 had a complete response to neoadjuvant chemotherapy, 3 of whom are alive >50 months from treatment compared with 2 patients showing GST-pi amplification. Neither responded to chemotherapy, and both died of disease <9 months from diagnosis. CONCLUSIONS: Using FISH, GST-pi amplification is a common event in head and neck squamous cell carcinoma and may be associated with cisplatin resistance and poor clinical outcomes in head and neck cancer patients treated with cisplatin-based therapy.     

Combined spectral karyotyping, comparative genomic hybridization, and in vitro apoptyping of a panel of Burkitt's lymphoma-derived B cell lines reveals an unexpected complexity of chromosomal aberrations and a recurrence of specific abnormalities in chemoresistant cell lines

The comprehensive cytogenetic profiles of a panel of 10 Burkitt's lymphoma (BL)-derived B cell lines, designated Akata, BL-28, BL-41, Daudi, DG-75, Mutu I, Mutu III, Namalwa, Rael, and Ramos, respectively, are reported herein. The unique origin of each cell line was established using multiplex quantitative fluorescence polymerase chain reaction (QF-PCR). Spectral karyotyping (SKY) revealed a large number of structural and numerical chromosomal aberrations, many of which had not been previously identified or resolved by conventional G-banding techniques. Notably, whereas all 10 cell lines harbored the hallmark translocation t(8;14)(q24;q32), no other common structural aberrations were identified, although translocations involving chromosomes 3, 13, and 17 were frequently seen. Moreover, analysis of chromosomal breakpoints by comparative genomic hybridization (CGH) revealed a number of recurring aberrations, such as gain of chromosomes 7 and 20, gains of regions at 2p, 3q, 13q and 16q, and losses at 3p, 4q and 17p. In addition, apoptyping (i.e. determination of in vitro responses to apoptosis stimulation) of the cell lines suggested specific association patterns between karyotypic changes (e.g. translocations involving 17p, and gains of portions of chromosomes 7 and 20) and resistance to the chemotherapeutic agent, etoposide. The current molecular cytogenetic characterization of 10 BL cell lines has thus identified several novel sites of rearrangements; moreover, the combined karyotyping and functional assessment (apoptyping) of these cell lines serves to enhance their utility in future studies aimed at gene discovery and gene function.     

Multiple chromosomal underrepresentations detected by interphase cytogenetics — possible prognostic markers in head and neck tumors?

Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.     

Genetic imbalances in preinvasive tissue of hypopharynx provide evidence for cytogenetic heterogeneity

Multiple chromosomal aberrations have been reported in head and neck squamous cell carcinoma (HNSCC). But less information is available on specific patterns of chromosomal amplifications which distinguish different areas of head and neck tumors. To elucidate genetic mechanisms causing the aggressive growth and high proliferation of hypopharyngeal squamous cell carcinoma (SCC), we performed reverse chromosome painting (RCP) on a total of eight hypopharyngeal SCC including invasive carcinoma and preinvasive tissue. Five hypopharyngeal invasive carcinomas showed amplifications on chromosome 3q. Furthermore, we detected gains on chromosomes 11q and 6p. Compared to the histologically classified preinvasive tissues, we found amplified alterations on chromosome 6p, 11q and 12q, but none of them showed gains on chromosome 3q. This observed heterogeneity in hypopharyngeal SCC might reflect a specific role of chromosome 3q as a late event in the highly invasive capacity of these SCC.     

Karyotypic characterization of papillary thyroid carcinomas.

BACKGROUND: Cytogenetic studies performed in papillary thyroid carcinoma (PTC) identified chromosome 10q rearrangements with breakpoints at 10q11.2 as the most frequent aberrations in these tumors. In the current study, the authors aimed to identify other chromosomal abnormalities nonrandomly associated with papillary thyroid carcinomas. METHODS: Cytogenetic analysis was performed on 94 papillary thyroid carcinomas after short-term culture of the tumors sterile fragments. RESULTS: Clonal chromosomal changes were found in 37 tumors (40%). Structural cytogenetic abnormalities were observed in 18 carcinomas. Chromosomes 1, 3, 7, and 10 were the most frequently involved in rearrangements. Pooled results of the breakpoints detected in these tumors, as well as those described in the literature, allowed the authors to verify as the most common breakpoint loci 1p32-36, 1p11-13, 1q, 3p25-26, 7q34-36, and 10q11.2. The correlation between the karyotype features of the 94 PTCs and the histologic data revealed that some PTC follicular variants were characterized by chromosomal aberrations commonly found in thyroid follicular adenomas: a del(11)(q13q13), a t(2;3)(q13;p35), and gains of chromosomes 3, 5, 7, 9, 12, 14, 17, and 20. In the tall cell PTC variant group, 4 of the 7 tumors presented clonal cytogenetic changes, 3 (75%) of which were characterized by anomalies of chromosome 2 that lead to a overrepresentation of the long arm of this chromosome. Noted also in these series was an association between complex karyotypes and tumors with poorly differentiated histiotypes. CONCLUSIONS: In this study, the authors report chromosome 1p32-36, 1p11-13, 3p25-26, and 7q32-36 as novel breakpoint cluster regions in PTC, and they suggest that there are cytogenetic changes preferentially associated with the follicular and tall cell PTC variants.     

Comparison of DNA Copy Numbers in Original Oral Squamous Cell Carcinomas and Corresponding Cell Lines by Comparative Genomic Hybridization

We analyzed regional DNA copy numbers in 4 oral squamous cell carcinomas (SCCs) by using comparative genomic hybridization, and compared them with those in cell lines derived from the SCCs. In the original tumors, DNA copy number increases were observed on chromosomes 5p (4/4 cases), 8q (4/4), 20p (3/4), 3q (2/4), 5q (2/4), 7p (2/4), 7q (2/4), 1ip (2/4), 11q (2/4) and 13q (2/ 4). Although most of these changes have been described previously for SCC tumors in the head and neck, the incidence of increases in 8q and 20p was much higher in the present study; this may be important in relation to cell line establishment, since 8q contains c- myc , which is involved in immortalization. No common chromosomal region with DNA copy number decreases was observed, except for 18q (2/4). When the original tumors and the cell lines were compared, their profiles were essentially similar with one exception. Further, there was no region that commonly changed in the cell lines, but not in the original tumors, suggesting that the DNA copy number changes observed in the cell lines mostly represent those of the original tumors.