Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract.

In contrast to low-grade B-cell lymphomas originating in the gastrointestinal (GI) tract, only few cytogenetic data are available for the large cell, highly malignant variants. We studied 31 large B-cell lymphomas of the GI tract by comparative genomic hybridization (CGH) and fluorescence in situ hybridization using specific DNA probes (FISH). The most frequent aberrations were gains of all or of parts of chromosomes 11 (11 cases), 12 (9 cases), 1q (4 cases), and 3q (4 cases). Losses of parts of chromosome 6q and of parts of the short arm of chromosome 17 (6 cases each) were found most frequently. In four cases a total of seven high-level DNA amplifications was detected. In two of these cases, involvement of specific protooncogenes (REL and MYC) was shown. Some genetic aberrations seemed to be associated with an inferior clinical course: patients with >/=2 aberrations had a significantly shorter median survival. Furthermore, all patients with gains of all or parts of chromosome arm 1q and with high-level DNA amplifications as well as seven of nine patients with gains of all or parts of chromosome 12 died of lymphoma. In conclusion, the pattern of chromosomal gains and losses in large B-cell lymphomas was different from data reported for low-grade (MALT) lymphomas of the stomach and bowel, especially with respect to the high incidence of partial gains of chromosome arm 11q and of all or parts of chromosome 12 and the low frequency of polysomy 3. In addition, our data suggest that chromosomal gains and losses detected by CGH and FISH may predict for the outcome of patients with this tumor entity.

High-level DNA amplifications are common genetic aberrations in B-cell neoplasms.

Gene amplification is one of the molecular mechanisms resulting in the up-regulation of gene expression. In non-Hodgkin's lymphomas, such gene amplifications have been identified rarely. Using comparative genomic hybridization, a technique that has proven to be very sensitive for the detection of high-level DNA amplifications, we analyzed 108 cases of B-cell neoplasms (42 chronic B-cell leukemias, 5 mantle cell lymphomas, and 61 aggressive B-cell lymphomas). Twenty-four high-level amplifications were identified in 13% of the patients and mapped to 15 different genomic regions. Regions most frequently amplified were bands Xq26-28, 2p23-24, and 2p14-16 as well as 18q21 (three times each). Amplification of several proto-oncogenes and a cell cycle control gene (N-MYC (two cases), BCL2, CCND2, and GLI) located within the amplified regions was demonstrated by Southern blot analysis or fluorescence in situ hybridization to interphase nuclei of tumor cells. These data demonstrate that gene amplifications in B-cell neoplasms are much more frequent than previously assumed. The identification of highly amplified DNA regions and genes included in the amplicons provides important information for further analyses of genetic events involved in lymphomagenesis.

Evaluating AIDS-related social skills in Anglo and Latino adolescents. Focus on assessment.

The purpose of this study was to examine the assessment of AIDS-related social skills (measured by role play) in Anglo and Latino adolescents (N = 383) and to explore ethnic and gender differences on these skills. Eight skills were assessed on five measures evaluating molar, molecular, verbal, and nonverbal dimensions of behavior. Interrelationships between skills and measurement dimensions were examined using factor analysis. Results revealed that Anxiety and Nonverbal Behavior each loaded across different skills on individual respective factors, whereas verbal content and assertiveness measures loaded by skill on separate factors. Differences in skill emerged between female and male, and Latino and Anglo youth. Preliminary social validity data were collected for the skills assessed. Social validity results were skill specific, with judges validating certain skills and certain measurement dimensions more than others. Implications for future assessment and intervention research of AIDS-related social skills are discussed.

High incidence of chromosomal imbalances and gene amplifications in the classical follicular variant of follicle center lymphoma.

The classical follicular variant of follicle center lymphoma (FCL-fo) is associated with the chromosomal translocation t(14;18)(q32;q21). However, the sole presence of this translocation is not sufficient for malignant transformation, as demonstrated by experiments in a transgenic mouse model. Most of the secondary changes, which play a central role in tumor development and progression and which are presumed to be of prognostic value, are gains and losses of chromosomal material. We analyzed 28 FCL-fo patients using comparative genomic hybridization (CGH). The most frequent imbalances were gains on chromosomes X, 7, 8, 12, and 18 as well as losses of material on chromosome arm 6q. For chromosomes X, 8, 12, and 18, the CGH data allowed further narrowing of the relevant subregions. In addition, novel high-level DNA amplifications were identified in five instances mapping to chromosome bands 1p36, 6p21, 8q24 (2 patients), and 12q13-14. Previously, such amplifications have been identified very rarely in lymphomas. In the 2 patients with amplifications mapping to chromosomal band 8q24, involvement of the MYC proto-oncogene in the amplification unit was demonstrated by Southern blot analysis. These data provide further entry points for studies to identify genes relevant for tumor progression in FCL-fo.

Chromosome imbalances in papillary renal cell carcinoma and first cytogenetic data of familial cases analyzed by comparative genomic hybridization.

We used comparative genomic hybridization to analyze 17 tumor samples from 11 patients with papillary renal cell carcinoma (RCC), including three patients with hereditary papillary RCC. Whereas the most frequent aberrations confirmed data obtained by banding analyses, copy number increases on 5q, which previously were considered characteristic of nonpapillary RCC, were identified in two cases. In two complex cases belonging to the same family, a characteristic pattern of chromosomal aberrations was found: five of the six imbalances present in the less complex case were included in the karyotype of the other case, suggesting a genetically determined mechanism resulting in genomic instability of specific chromosomes or chromosomal subregions and/or selection of specific mutations.

Identification of genetic imbalances in malignant lymphoma using comparative genomic hybridization.

In comparison to leukemias, the clinical relevance of chromosomal aberrations in non-Hodgkin's lymphoma (NHL) is not as well understood. This is primarily due to limitations of chromosomal banding techniques which have been the central methods for cytogenetic analysis. These techniques depend on the availability of fresh tumor tissue and the examination of metaphase cells which may not be representative for the major cell clone in vivo. In contrast, the new technique of comparative genomic hybridization (CGH) allows researchers to obtain a comprehensive view of chromosomal gains and losses by analyzing tumor DNA, which can be prepared from archival tissue samples. Results of CGH studies in three different types of lymphoproliferative disorders are outlined in this paper demonstrating that: (1) in chronic B cell leukemias, chromosomal aberrations are missed by banding analysis in a high proportion of cases, (2) CGH on paraffin-embedded tissue samples can be used for cytogenetic analysis within clinical multicenter trials and (3) DNA amplifications are more frequent in NHL than previously assumed. Thus, it can be expected that CGH will contribute both to the understanding of pathogenetic mechanisms and the identification of clinically relevant chromosome aberrations in NHL.

Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses.

In chronic B-cell leukemias, fluorescence in situ hybridization has greatly improved the ability to detect certain chromosomal aberrations, as cells in all phases of the cell cycle are analyzed. To obtain a comprehensive view of chromosomal gains and losses, we applied the recently developed technique of comparative genomic hybridization (CGH) to 28 patients with chronic B-cell leukemias. CGH results were compared with those obtained by chromosome banding analysis and interphase cytogenetics. In 19 of the 28 cases, chromosomal imbalances were detected, including amplified DNA sequences in three instances. The most common aberrations included gains of chromosomal material on 8q and 12 as well as losses of 6q, 11q, 13q, and 17p. In 13 cases, CGH revealed chromosomal gains and losses not detected by banding analysis. In 8 of these 13 cases, discrepancies were further investigated using other methods, and in all instances, the CGH findings were confirmed. A limitation of detecting small deleted regions by CGH was found in one example of 18p. In conclusion, our data show that the results of banding analysis in chronic B-cell leukemias often do not reflect the chromosomal changes in the predominant cell clone. This may be one explanation for the as yet poor correlation between cytogenetic findings and clinical course in this group of neoplasms.