Minimal regions of chromosomal imbalance in retinoblastoma detected by comparative genomic hybridization

Mutation of both alleles of the retinoblastoma gene (RB1) initiate oncogenesis in developing human retina, but other common genomic alterations are present in the tumors. In order to sublocalize the altered genomic regions, 50 retinoblastoma tumors were examined by comparative genomic hybridization (CGH). The minimal regions most frequent gained were 1q31 (52%), 6p22 (44%), 2p24-p25 (30%) and 13q32-q34 (12%). The minimal region most frequently lost was 16q22 (14%). The overall total number of gains or losses evident on CGH was significantly greater in those tumors with either or both 6p or 1q gain, than in tumors with neither 6p nor 1q gain suggesting that chromosomal instability may be associated with acquisition of these changes. Genes mapping to 6p22 and 1q31 may be important in tumor development in retina subsequent to the loss of RB1 alleles.     

Genomic aberrations in 80 cases of primary glioblastoma multiforme: Pathogenetic heterogeneity and putative cytogenetic pathways

Screening the whole glioblastoma multiforme (GBM) genome for aberrations is a good starting point when looking for molecular markers that could potentially stratify patients according to prognosis and optimal treatment. We investigated 80 primary untreated GBM using both G‐banding analysis and high‐resolution comparative genomic hybridization (HR‐CGH). Abnormal karyotypes were found in 83% of the tumors. The most common numerical chromosome aberrations were +7, ?10, ?13, ?14, ?15, +20, and ?22. Structural abnormalities most commonly involved chromosomes 1 and 3, and the short arm of chromosome 9. HR‐CGH verified these findings and revealed additional frequent losses at 1p34‐36, 6q22‐27, and 19q12‐13 and gains of 3q26 and 12q13‐15. Although most karyotypes and gain/loss patterns were complex, there was also a distinct subset of tumors displaying simple karyotypic changes only. There was a statistically significant association between trisomy 7 and monosomy 10, and also between +7/?10 as putative primary aberrations and secondary losses of 1p, 9p, 13q, and 22q. The low number of tumors in the rarer histological tumor subgroups precludes definite conclusions, but there did not seem to be any clear‐cut cytogenetic‐pathological correlations, perhaps with the exception of ring chromosomes in giant cell glioblastomas. Our findings demonstrate that although GBM is a pathogenetically very heterogeneous group of diseases, distinct genomic aberration patterns exist. © 2009 Wiley‐Liss, Inc.     

Chromosome DNA imbalances in human astrocytic tumors: A comparative genomic hybridization study of 63 Chinese patients

Astrocytic tumors are the most frequent primary brain neoplasms. They are clinically characterized by wide variations in histology. Analysis of chromosome DNA imbalance may help to advance diagnosis, grading, and classification, and to determine appropriate therapeutic approaches for tumors of astrocytic lineages. Comparative genomic hybridization (CGH) provides comprehensive information about chromosome DNA aberrations, and is an important technique for evaluating the differences at genomic levels among the same or different grade tumors. In this study, 63 astrocytic tumors of Chinese patients were screened by CGH, and the relationship between their chromosome DNA imbalances and the histopathological classification, grading, and clinical features was analyzed. Most tumors showed genomic copy aberrations detected by CGH. The most frequent abnormalities were regional gains in chromosome 1q and 7p; regional losses in chromosome 1p, 2q, 4q, 6p, 10q, 12q, 15q, 19q, and 22q were also frequently observed. The gain of 1q and the loss of 15q were relevant to the histological types and grades of WHO classification. The losses of 4q and 10q correlated with age in the group of anaplastic astrocytoma, which was unreported in the literature. This study confirmed that chromosomal aberrations, such as +1q, −4q, −10q, +7p, and −15q possibly contributed to the pathogenesis of these tumors. Our data was the first report on the chromosomal aberrations of astrocytic tumors of Chinese patients.     

Microdissection, DOP-PCR, and comparative genomic hybridization of paraffin-embedded familial prostate cancers

There is a clear genetic component to prostate cancer susceptibility. Regions reported to be linked to prostate cancer include 1q24-25 (HPC-1), 1q42.2-43, and Xq27-28. There is limited genetic information on familial prostate tumors. We used the Utah Population Database to identify familial prostate cancer cases and selected 35 cases from high-risk families. Tissue blocks containing discernable tumor were available from 19 cases; 13 of these yielded adequate specimens for analysis. Six cases came from families with linkage to HPC-1, 3 were known to have linkage to Xq27-28, and 4 had no linkage to a known locus; 7 cases were analyzed from patients who showed no known linkage (sporadic tumors) as controls. These paraffin-embedded tumors were laser microdissected, degenerate oligonucleotide (DOP)-amplified, and labeled for fluorescence detection by comparative genomic hybridization (CGH). Loss of 7q, 10q, and 16q and gain of 8q were common abnormalities present in both familial and sporadic tumors. Distinctive abnormalities included loss of 3p12-3p22 in 3 of 6 HPC-7-linked cases and in 2 of 3 X-linked cases and gain of 6q11-6q21 in 2 each of HPC-1 and X-linked tumors. In conclusion, laser microdissection, DOP-PCR, and CGH is a feasible method for analysis of paraffin-embedded prostate tumors. This study provides preliminary data suggesting that familial prostate cancer harbors some unique genetic changes when compared with sporadic prostate tumors.     

Detection of chromosome imbalances in retinoblastoma by parallel karyotype and CGH analyses

We have studied a series of 20 primary retinoblastomas by karyotypic analysis and comparative genomic hybridization (CGH), to perform an exhaustive evaluation of chromosome imbalances in this tumor. In addition, 4 tumors were studied by CGH only. On the whole, CGH results were largely in agreement with those of karyotypic analysis and with known cytogenetic data. The most frequent imbalances were +6p (13/24 cases), +1q (12/24), -16/-16q (11/24), and +2p (9/24). Recurrent high-level amplifications were observed in 2p23-25 and 1q21. Amplification of 2p23-25, present in 4 cases among which 3 showed double-minute chromosomes, was related to MYCN amplification, as demonstrated by FISH and PCR. No evident correlation was found in this small series between any of the imbalances identified and either the differentiation or the histoprognostic risk.     

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.     

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Chromosomes in kidney, ureter, and bladder cancer

Although Wilms tumor has been a favored subject for cytogenetic investigation, little is known about chromosomes in adult urinary tract cancers. For this reason, we excluded Wilms' tumor and studied a series of 32 adult urinary tract tumors. Nineteen tumors had detectable autosomal abnormalities. Each of ten renal tumors (consisting of eight renal cell and two transitional cell carcinomas) had three or more chromosome abnormalities. Two candidates for primary chromosome changes in renal cancer are rearrangement of 3p14 and an unbalanced translocation with breakpoints of 5q13 and 14q22. Trisomy 20 is a frequent secondary change. Other nonrandom changes in renal cancer are rearrangements of 1q and +7, -8, -9, -14, -15, +16, and deletions of 17p. Eight bladder and a ureter tumor were all transitional cell carcinomas. Two bladder and the ureter tumor had only one detectable abnormality: deletions of 10q24 and 21q22 and +7, respectively. Other nonrandom bladder changes were -9, +13, +15, and +20. From a cytogenetic standpoint, adult urinary tract tumors appear to be chromosomally complex but critical consistencies are emerging.     

Novel genomic imbalances in B-cell splenic marginal zone lymphomas revealed by comparative genomic hybridization and cytogenetics

Splenic marginal zone lymphoma (SMZL) has recently been recognized in the World Health Organization classification of hematological diseases as distinct type of non-Hodgkin's lymphoma. In contrast to the well-established chromosomal changes associated with other B-cell non-Hodgkin's lymphoma, few genetic alterations have been found associated with SMZL. The aim of our study was to analyze by comparative genomic hybridization (CGH) the chromosomal imbalances in 29 patients with SMZL and to correlate these findings with clinical and biological characteristics and patient outcome. In 21 cases, cytogenetic studies were simultaneously performed. Most of the patients (83%) displayed genomic imbalances. A total of 111 DNA copy number changes were detected with a median of four abnormalities per case (range, 1 to 12). Gains (n = 92) were more frequent than losses (n = 16), while three high-level amplifications (3q26-q29, 5p11-p15, and 17q22-q25) were observed. The most frequent gains involved 3q (31%), 5q (28%), 12q and 20q (24% each), 9q (21%), and 4q (17%). Losses were observed in 7q (14%) and 17p (10%). SMZL patients with genetic losses had a shorter survival than the remaining SMZL patients (P < 0.05). In summary, chromosomal imbalances in regions 3q, 4q, 5q, 7q, 9q, 12q, and 20q have been detected by CGH in SMZL. Patients with SMZL displaying genetic losses by CGH had a short survival.     

Constitutional genomic instability, chromosome aberrations in tumor cells and retinoblastoma

Although retinoblastoma (Rb) is initiated as a result of biallelic inactivation of the RB1 gene, additional genetic events (M3) in tumor cells are indicative of their role in the full transformation of retinal cells. We investigated the constitutional genetic instability by fragile site (FS) expression studies and checked its relationship with loci of tumor cytogenetics in a series of 36 retinoblastoma patients (34 nonfamilial and 2 familial cases). Tumor cytogenetics revealed -13/+13, del/t(13)(q14) (50%), +1/del/t(1p/q) (65%), +6/i(6p) (60%), and del(16)(q13)/(q22 approximately q23) (60%). Conventional cytogenetics in leukocytes revealed constitutional del(13q14) in five unilateral Rb (URB) and one trilateral Rb (TRB). Constitutional del(16)(q22) and t(6;12) were also identified in two cases. Constitutional FS analysis showed a significant increase in the cellular fragility, with high prevalence at 13q14, 3p14, 6p23, 16q22 approximately q23, and 13q22 loci in retinoblastoma patients (P<0.05). Patients with constitutional del(13)(q14) demonstrated higher fragility than those with normal constitution. A strong correlation between loci of constitutional FSs and loci of recurrent chromosomal abnormalities in tumors strengthen and support the proposal that FS loci present as inherent genomic instability in retinoblastoma. The chromosomal changes and resultant genetic mutations, along with RB1 mutation events, probably contribute synergistically to the development and progression of Rb malignancy. Implementation of fluorescence in situ hybridization to nonfamilial Rb on a large scale (113 cases) could detect constitutional RB1 deletion in 12.3% of cases, with equally higher incidence in URB (14.7%) and bilateral Rb (13.6%), demonstrating that the true prevalence of patients with predisposition to RB1 mutation in sporadic URB is definitely higher in our populations. Also, higher incidence of constitutional RB1 deletion mosaicism in unilateral than in bilateral Rb indicates that the constitutional genetic mosaicism in URB should be given serious consideration during genetic counseling.     

Genetic changes and clonality relationship between primary colorectal cancers and their pulmonary metastases--an analysis by comparative genomic hybridization

About 10% of colorectal carcinoma patients develop pulmonary metastases during their lifetime. We address whether and how the chromosomal abnormalities differ between the primary cancers and their metastatic counterparts, what the clonality relationship (CR) is between them, and whether certain genomic aberrations contribute to this disease progression. Comparative genomic hybridization (CGH) experiments were performed on 18 paired samples of primary and pulmonary metastases obtained from patients who had undergone two consecutive surgeries and from whom clinical data had been collected. The CGH profiles also were used as indexes for determining the CR between the cancers. The overall CGH abnormality profiles were similar for the primary colorectal carcinomas and their pulmonary metastases. Frequent gains were found on chromosome arms 20q, 8q, 13q, and 7q, whereas common losses were found on 18q, 8p, and 18p. The pulmonary metastases, however, contained more CGH abnormalities than did the primary carcinomas (total aberration events per tumor: 12.6 +/- 5.0 vs. 8.3 +/- 5.7, respectively, P = 0.024; gains: 7.6 +/- 3.1 vs. 5.1 +/- 3.5, respectively, P = 0.036; losses: 5.0 +/- 2.8 vs. 3.3 +/- 2.9, respectively, P = 0.076). Comparing CGH profiles between individual primary and metastasis pairs, we found that 10 of the 18 (56%) paired samples examined exhibited a high degree of CR, indicating that they were likely to have originated from the same clone and/or that not many additional chromosomal changes had occurred in the metastases, except for 4q loss, whose incidence was much higher in the metastases than in the primaries (60% vs. 10%; P = 0.030). Also, the primary tumors of the high-CR group carried more genomic aberrations, especially 8p loss, than did the primary tumors in the low-CR group. We found more chromosomal changes associated with the pulmonary metastases of colorectal cancer compared with the corresponding primary tumors. We concluded that primary cancers containing more genomic lesions, especially 8p losses, are more likely to metastasize to the lungs. Loss of 4q is potentially a supplementary factor contributing to the dissemination of this disease.     

Cytogenetic features of twenty-six primary breast cancers.

Tumor preparations from 26 primary breast cancers were studied cytogenetically with G-banding, using a direct technique, synchronized short-term culture, or both. Two tumors had normal karyotypes, and 24 (92%) had chromosomal abnormalities. Nineteen tumors had chromosome 1 rearrangements, with 10 cases (40%) displaying distal short arm translocations (1p36). Other frequent breakpoints occurred at 3p21, 6q22-27, 11q21-25, 16q22-24, 17p, and 19q13. To seek primary rather than secondary cytogenetic changes, attention was directed toward tumors with diploid-range karyotypes (32-57 chromosomes per cell). Of four such tumors, three exhibited nonrandom involvement of chromosome 16q22. This, together with previously reported data, suggests that deletion or rearrangement of chromosome 16q21-24 may be a primary or specific event in a subset of breast cancers.     

Cytogenetic subtype involving chromosome 13 in lipoma. Report of three cases

We report three lipomas with rearrangements of chromosome 13. The karyotype of the tumors studied were 45,XX,-8,+der(8)t(8;13)(q22;q12),del(10)(p12),-13; 46,XY,del(13)(q12q22), and 46,XY,t(11;12)(q23;q13),del(13)(q12q22), respectively, revealing common involvement of band 13q12 in the rearrangement. Three other lipomas with aberrations of bands 13q12-q13 have been reported, suggesting that such tumors with abnormalities of chromosome 13 could represent a subgroup of lipoma in addition to those already reported with abnormalities of chromosomes 12q and 6p. The rearrangements of #13 in all these cases also involved loss of the band 13q14 to which the antioncogene associated with retinoblastoma and osteosarcoma is localized. Detailed clinical, histopathologic, and molecular studies should help to further characterize the various cytogenetically defined subgroups of lipoma.     

Genome-wide appraisal of thyroid cancer progression

Several lines of evidence suggest that follicular cell-derived thyroid cancers represent a continuum of disease that progresses from the highly curable well-differentiated thyroid cancers to the universally fatal anaplastic cancers. However, the genetic mechanisms underlying thyroid cancer progression remain ill defined. We compared the molecular-cytogenetic profiles derived from comparative genomic hybridization (CGH) analysis of major histological variants of thyroid cancer to define genetic variables associated with progression. Overall, a sequential increase in chromosomal complexity was observed from well-differentiated papillary thyroid cancer to poorly differentiated and anaplastic carcinomas, both in terms of the presence of CGH detectable abnormalities (P = 0.003) and the median number of abnormalities per case (P < 0.001). The presence of multiple abnormalities common to all thyroid cancer variants, including gains of 5p15, 5q11-13, 19p, and 19q and loss of 8p, suggests that these tumors are derived from a common genetic pathway. Gains of 1p34-36, 6p21, 9q34, 17q25, and 20q and losses of 1p11-p31, 2q32-33, 4q11-13, 6q21, and 13q21-31 may represent secondary events in progression, as they were only detected in poorly differentiated and anaplastic carcinomas. Finally, recurrent gains at 3p13-14 and 11q13, and loss of 5q11-31 were unique to anaplastic carcinomas, suggesting they may be markers for anaplastic transformation. Our data suggests that the development of chromosomal instability underlies the progression to more aggressive phenotypes of thyroid cancer and sheds light on the possible genomic aberrations that may be selected for during this process.     

Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization

We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy number changes in 67 synovial sarcomas of both monophasic and biphasic histological subtypes. Changes (mean among aberrant cases: 4.7 aberrations/tumor; range: 1–17), affecting most often entire chromosomes or chromosome arms, were detected in 37 sarcomas (55%). Gains and losses were distributed equally, but different chromosomes were affected with variable frequencies. The most frequent aberrations, each detected in 9–11 of 67 tumors, were gain of 8q and gain at 12q (12q14-15 and 12q23-qter), loss of 13q21-31, and loss of 3p. Other frequent changes (in 7 or 8 cases) included gains at 2p, 1q24-31, and 17q22-qter, and losses at 3cen-q23 and 10q21. High-level amplifications were seen in 7 cases. A total of 16 regions were detected. Two of them, 8p12-qter and 21q21-qter, seen in 4 and 2 tumors, respectively, were recurrent. No aberrations specific to histological subtype were identified. However, genetic changes in the monophasic tumors were more complex and numerous (mean among aberrant cases: 5.3 aberrations/tumor; range: 1–17) than in the biphasic tumors (mean: 2.5 aberrations/tumor; range: 1–5), and high-level amplifications occurred more frequently. All but 1 of the sarcomas showing high-level amplification were of the monophasic subtype. These findings may reflect differences in the pathogenesis and biological behavior of both histological subtypes of synovial sarcoma. Genes Chromosomes Cancer 23:213–219, 1998. © 1998 Wiley-Liss, Inc.     

DNA copy number changes detected by comparative genomic hybridization and their association with clinicopathologic parameters in breast tumors

The purpose of this study was to use comparative genomic hybridization (CGH) to screen breast tumors for copy number changes: 22 ductal, 9 lobular, 7 mixed, 2 micropapillary carcinomas, and 2 ductal carcinoma in situ were studied and various regional genomic imbalances were detected. The majority of the aberrations identified in this study were in line with previous CGH findings. The most frequent DNA sequence copy number changes were 1q, 8q, and 20q gains. The frequency of 16q losses was significantly higher in lobular carcinomas. The nodal involvement was 10 times higher in cases showing losses of 13q than in cases having normal peak profile at this region. Estrogen receptor positivity was significantly higher in cases displaying 20q gains and 16q losses. Unambiguous high-level DNA amplifications have also been detected. These mapped to 4q31, 6q21 approximately q22, 8q21 approximately q24, 8p11.2 approximately p12, 11q13, 15q24 approximately qter, 20q13.1 approximately qter, and 20q12 approximately qter chromosomal locations. Our results highlight several chromosomal regions that may be important in the molecular genetics of distinct clinicopathologic breast cancer subgroups.     

Comparative genomic hybridization detects specific cytogenetic abnormalities in pediatric ependymomas and choroid plexus papillomas

Pathogenesis and genetic abnormalities of ependymomas are not well known and differential diagnosis with choroid plexus tumors may be difficult when these tumors are located in the ventricles. We analyzed 16 samples of primary pediatric ependymomas and seven choroid plexus tumors for significant gains or losses of genomic DNA, using comparative genomic hybridization (CGH). Four ependymoma samples were obtained after surgery for relapse, including one patient whose tumor was analyzed at diagnosis and at first and second relapses. Three out of 16 ependymomas and none of the choroid plexus tumors appeared normal by CGH. In the remaining ependymomas, the number of regions with genomic imbalance was limited. The most frequent copy number abnormality in ependymomas was 22q loss. In one patient from whom multiple samples could be analyzed during tumor progression, no abnormality was present at diagnosis; gain of chromosome 9 and loss of 6q were observed at first relapse and, at second relapse, additional genomic imbalances were loss of 3p, 10q, and chromosome 15. In choroid plexus tumors, recurrent abnormalities were gains of chromosome 7 and region 12q. The recurrent chromosomal abnormalities were clearly different between ependymomas and choroid plexus papillomas (CPP). Recurrent loss of 22q suggests that this region harbors tumor suppressor genes important in the pathogenesis of ependymomas; however, other pathogenic pathways may exist involving 6q and chromosome 10 losses or gain of 1q and chromosome 9. CPP can be distinguished from ependymoma on the basis of CGH abnormalities.     

Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology

Pheochromocytomas and abdominal paragangliomas are rare, catecholamine-producing tumors that arise from the chromaffin cells derived from the neural crest. We used comparative genomic hybridization (CGH) to screen for copy number changes in 23 pheochromocytomas and 11 abdominal paragangliomas. The pattern of copy number changes was similar between pheochromocytomas and paragangliomas, with the most consistent finding being loss of 1cen-p31, which was detected in 28/34 tumors (82%). Losses were also found on 3q22–25 (41%), 11p (26%), 3p13–14 (24%), 4q (21%), 2q (15%), and 11q22–23 (15%), and gains were detected on 19p (26%), 19q (24%), 17q24-qter (21%), 11cen-q13 (15%), and 16p (15%). Losses of 1p and 3q were detected in the majority of tumors, whereas gains of 19p and q, 17q, and 16p were seen only in tumors with six or more CGH alterations. This progression of genetic events did not correspond with the conversion to a malignant phenotype. CGH alterations involving chromosome 11 were more frequent in the malignant tumors, compared with the benign tumors (9/12 versus 3/16). In summary, we propose that pheochromocytomas and abdominal paragangliomas, which share many clinical features, also have a common genetic origin and that the loss of 1cen-p31 represents an early and important event in tumor development.     

Chromosomal imbalances: a hallmark of tumour relapse in primary cutaneous CD30+ T-cell lymphoma

Primary cutaneous CD30+ large T-cell lymphoma (CD30+ CTCL) is a subset of non-epidermotropic primary cutaneous T-cell lymphoma. Although frequent spontaneous regression may be observed, skin relapses occur frequently. Cytogenetic abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and relapses remain unknown. The identification of recurrent cytogenetic abnormalities is hampered by difficulty in culturing tumours and the lack of CD30+ CTCL serial studies comparing genetic changes both at diagnosis and at relapse. The purpose of this study was to investigate the cytogenetic abnormalities present in a series of 13 CD30+ CTCL samples obtained from nine patients fulfilling both EORTC and WHO diagnostic criteria, by the use of comparative genomic hybridization (CGH). CGH analysis revealed a non-random distribution of genetic imbalances between relapsing and non-relapsing disease. In relapsing disease, chromosomal abnormalities were detected both in the primary tumour and in relapses. The mean number of changes in non-relapsing disease was 0.33 (range 0-1), compared with 6.29 (range 1-16) in relapsing disease. The recurrent chromosomes involved in relapsing disease were chromosomes 6 (86%), 9 (86%), and 18 (43%). While chromosome 9 was mostly affected by gain, chromosomes 6 and 18 mainly contained regions of loss, exclusively on 6q and 18p. The common regions of deletion were 6q21 and 18p11.3. In one patient, we successfully cultured tumour cells from a skin biopsy from a second relapse. The G-banded karyotype was concordant with both CGH and fluorescence in situ hybridization (FISH) results. Although further studies are required to strengthen these data, this CGH analysis demonstrates chromosomal imbalances that may be involved in the pathogenesis of relapsing CD30+ CTCL.     

Amplification of 2p13-16 in a case of extranodal large cell diffuse B-cell lymphoma

Comparative genomic hybridisation (CGH) allows to detect genetic abnormalities associated with poor prognosis in subset of patients with diffuse large B-cell lymphoma (DLBCL). Amplification of 2p13-16 represents an adverse genetic sign especially in extranodal DLBCL. In the present case, 2p13-16 amplification was revealed by CGH in extranodal DLBCL. It was localized in the mesentery and remained resistant to the chemotherapy (CHOP). A patient, 72-year-old female, died 10 weeks after the diagnosis had been made. Rapid lethal course of the disease confirms poor outlook for patients with 2p13-16 and supports a role of CGH as a sensitive method in prognosis for patients with DLBCL.