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Biomedical subjects

Reiner Siebert

Publications and source records attributed to Reiner Siebert.

At least 55 records · Page 3Linked to original sources
PubMed2004

Screening 500 unselected neurofibromatosis 1 patients for deletions of the NF1 gene.

A total of 500 unselected unrelated neurofibromatosis 1 (NF1) patients were screened for deletions of the NF1 gene. After excluding 67 patients with known intragenic NF1 mutations, the remaining 433 were genotyped using six intragenic and one distal microsatellite marker for the NF1 gene. A total of 28 patients were hemi- or homozygous for all seven markers and were thus considered as candidates for NF1 deletion with a calculated probability of 99.99%. Metaphase or interphase cells were available from 23 of these 28 individuals for molecular cytogenetics. Fluorescence in situ hybridization (FISH) confirmed an NF1 deletion in 22 (96%) of the 23 patients. Thus, a constitutional deletion of the NF1 gene is responsible for the disease phenotype in at least 4.4% of the 500 unselected NF1 patients. Genotyping using multiple microsatellite markers may provide a simple, inexpensive, and efficient strategy for screening deletions of the NF1 gene, and can as well be applied for other large genes.

Female↗
PubMed2004

Homogeneous immunophenotype and paucity of secondary genomic aberrations are distinctive features of endemic but not of sporadic Burkitt's lymphoma and diffuse large B-cell lymphoma with MYC rearrangement.

The present study has compared immunohistological marker expression profiles and genomic imbalances in seven African endemic Burkitt's lymphomas (eBLs) with those in ten European B-cell lymphomas with MYC rearrangement as shown by fluorescence in situ hybridization (FISH) analysis. eBLs showed a typical histomorphology and a homogeneous immuno-profile: CD10+, CD38+, CD77+, bcl-2-, and IgM+. Epstein-Barr virus (EBV) DNA was present in all cases. On comparative genomic hybridization (CGH), only three out of six eBLs showed imbalances (median number of imbalances = 2), with gains on chromosome 17 in two eBLs. The European lymphomas were all highly proliferating, with a Ki-67 index of at least 90%, and included seven with morphology typical of sporadic Burkitt's lymphoma (sBL) and three immunoblastic diffuse large B-cell lymphomas with MYC rearrangement (MYCre+DLBCL). In contrast to eBL, the immuno-profiles of the European lymphomas were less homogeneous and inconsistent for CD10, CD38, CD77, IgM and bcl-2 expression. EBV DNA was not detected. In five of seven sBLs, CGH showed a higher number of imbalances (median = 6), with recurrent gains on chromosome 1q (3/7) and losses on 12q and 17p (2/7), whereas all three MYCre+DLBCLs had fewer imbalances (median = 4), with gains on 17q in two of three lymphomas. It is concluded that eBL has a homogeneous immunohistology and few secondary genomic aberrations, whereas MYC-rearranged and highly proliferating European B-cell lymphomas are a heterogeneous group that includes sBL and a subgroup of diffuse large B-cell lymphomas.

Adolescent↗
PubMed2004

Folate-sensitive fragile site FRA10A is due to an expansion of a CGG repeat in a novel gene, FRA10AC1, encoding a nuclear protein.

Fragile sites appear visually as nonstaining gaps on chromosomes that are inducible by specific cell culture conditions. Expansion of CGG/CCG repeats has been shown to be the molecular basis of all five folate-sensitive fragile sites characterized molecularly so far, i.e., FRAXA, FRAXE, FRAXF, FRA11B, and FRA16A. In the present study we have refined the localization of the FRA10A folate-sensitive fragile site by fluorescence in situ hybridization. Sequence analysis of a BAC clone spanning FRA10A identified a single, imperfect, but polymorphic CGG repeat that is part of a CpG island in the 5'UTR of a novel gene named FRA10AC1. The number of CGG repeats varied in the population from 8 to 13. Expansions exceeding 200 repeat units were methylated in all FRA10A fragile site carriers tested. The FRA10AC1 gene consists of 19 exons and is transcribed in the centromeric direction from the FRA10A repeat. The major transcript of approximately 1450 nt is ubiquitously expressed and codes for a highly conserved protein, FRA10AC1, of unknown function. Several splice variants leading to alternative 3' ends were identified (particularly in testis). These give rise to FRA10AC1 proteins with altered COOH-termini. Immunofluorescence analysis of full-length, recombinant EGFP-tagged FRA10AC1 protein showed that it was present exclusively in the nucleoplasm. We show that the expression of FRA10A, in parallel to the other cloned folate-sensitive fragile sites, is caused by an expansion and subsequent methylation of an unstable CGG trinucleotide repeat. Taking advantage of three cSNPs within the FRA10AC1 gene we demonstrate that one allele of the gene is not transcribed in a FRA10A carrier. Our data also suggest that in the heterozygous state FRA10A is likely a benign folate-sensitive fragile site.

Alleles↗
PubMed2004

Burkitt's lymphoma of the stomach: a case report with molecular cytogenetic analysis.

In 1974, a 28-year-old man presented with a 12 cm sized ulcerated tumor involving the middle third of the stomach, which was originally diagnosed as "lymphosarcoma". Clinical recurrence of the lymphoma resulted in rapidly progressing disease and the patient died 4 months after initial diagnosis. Retrospective work-up of the 29-year-old tumor blocks revealed the typical histologic appearance and phenotype (CD20, CD10, BCL-6 positive) of Burkitt's lymphoma (BL) with a proliferation rate of 95%. By fluorescence in situ hybridization (FISH). the tumor cells were shown to harbor an IGH-MYC fusion indicating the presence of the hallmark Burkitt-translocation t(8;14)(q24;q32). Considering the typical clinical features of BL requiring appropriate treatment regimes the case presented here highlights the importance of modern histopathologic and molecular cytogenetic techniques for the proper classification of such rare lymphomas presenting at atypical sites.

Adult↗
PubMed2004

Chromosomal aberration patterns differ in subtypes of primary cutaneous B cell lymphomas.

The diagnostic and prognostic importance of recurrent chromosomal aberrations in systemic B cell lymphoma is well documented. In contrast, limited data exist on genetic changes in primary cutaneous B cell lymphoma. In this study we investigated chromosomal aberration patterns in two types of primary cutaneous B cell lymphoma with a different clinical behavior. Twenty-two primary cutaneous B cell lymphomas, including nine follicle center cell lymphomas and 13 large B cell lymphomas of the leg, were analyzed by comparative genomic hybridization and in part by fluorescence in situ hybridization. The most frequent imbalances detectable were gains in 18q (eight of 22), 1q (six of 22), 7 (six of 22), 12q (six of 22), or Xp (four of 22), and losses in 6q (four of 22). In contrast to large B cell lymphomas of the leg, primary cutaneous follicle center cell lymphomas had fewer imbalances and lacked translocations affecting the IGH locus. Gains in 18q (eight of 13) and losses in 6q (four of 13) as well as breakpoints within the IGH locus (six of 11) were restricted to the large B cell lymphomas of the leg subtype. Translocation t(14; 18) was excluded in 16 primary cutaneous B cell lymphomas of both subtypes that were studied by fluorescence in situ hybridization. These results suggest that primary cutaneous follicle center cell lymphoma and large B cell lymphoma of the leg are characterized by different chromosomal aberration patterns, which in part might determine the different clinical course of these malignancies.

Adult↗
PubMed2003

Expression of the LGI1 gene product in astrocytic gliomas: downregulation with malignant progression.

Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may involve the LGI1/epitempin gene, which is located in chromosomal region 10q23 approximately 24 and has been proposed to encode a tumor suppressor inactivated in the progression of brain tumors. Nevertheless, so far no data are available demonstrating that the reduced expression of the LGI1 transcript in high-grade astrocytic tumors indeed results in a decreased level of LGI1 protein in the tumor cells. Thus, the aim of the present study was to analyze the expression of the LGI1 protein in a series (ten of each) of pilocytic astrocytomas, astrocytomas [World Health Organization (WHO) grade II], anaplastic astrocytomas (WHO grade III), and glioblastoma multiforme (WHO grade IV). Immunohistochemistry demonstrated a strong expression of the LGI1 protein in normal brain tissue as well as in the majority of pilocytic astrocytomas and astrocytomas (WHO grade II). In anaplastic astrocytomas, the number of tumor cells expressing LGI1 decreased, while LGI1 expression was completely absent from the glioblastomas of this series. This highly significant reduction of LGI1 protein expression in the progression of astrocytic brain tumors lends further support to the hypothesized function of LGI1 as a type-II tumor suppressor gene in glioma pathogenesis.

Adolescent↗
PubMed2003

ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.

Expression of ALK protein by lymphoid cells and the description of variant anaplastic lymphoma kinase (ALK) translocations have typically been restricted to cases of T-cell and null anaplastic large-cell lymphoma (ALCL). All such cases result from a novel fusion created by the ALK gene on chromosome 2p23 and NPM on 5q35 or other variant translocation partners. A rare variant of diffuse large B-cell lymphoma (DLBCL), originally described in 1997, was thought to overexpress full-length ALK in contrast to a chimeric protein characteristic of ALCL. However, full-length ALK protein lacks tyrosine kinase activity and thus the mechanism of oncogenesis has remained elusive. We describe 6 cases of ALK+ DLBCL characterized by a simple or complex t(2;17)(p23;q23) involving the clathrin gene (CLTC) at chromosome band 17q23 and the ALK gene at chromosome band 2p23. All cases were studied using fluorescence in situ hybridization (FISH), complemented in one case with standard cytogenetic analysis, multicolor karyotyping (M-FISH), and reverse transcriptase-polymerase chain reaction. These results clearly demonstrate that most cases of ALK+ DLBCL share the same mechanism of deregulated ALK expression. Moreover, these results demonstrate the presence of CLTC-ALK fusions in these tumors and extend the list of diseases associated with this genetic abnormality to include classical T-cell or null ALCL, ALK+ DLBCL, and inflammatory myofibroblastic tumors.

Anaplastic Lymphoma Kinase↗
PubMed2003

Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H pylori in gastric MALT lymphoma.

t(11;18)(q21;q21) is a specific chromosomal translocation associated with mucosa-associated lymphoid tissue (MALT) lymphoma. It fuses the amino terminal of the API2 gene to the carboxyl terminal of the MALT1 gene and generates a chimeric fusion product. Although the translocation is frequently detected in gastric and pulmonary MALT lymphoma, its incidence in MALT lymphomas from other sites is largely unknown. It also remains unknown whether the occurrence of the translocation is influenced by the nature of preceding diseases associated with MALT lymphomas. We screened for t(11; 18)(q21;q21) in 417 cases of MALT lymphoma from 8 major sites by reverse transcription-polymerase chain reaction. t(11;18)(q21;q21) was found at highest frequencies in MALT lymphomas from the lung (38%) and stomach (24%), and at moderate frequencies in those from the conjunctiva (19%) and orbit (14%). However, the translocation was found only rarely in MALT lymphomas from the salivary gland (1%) and was absent in those from the thyroid, skin, liver, and other rare sites, and in immunoproliferative small intestinal disease (IPSID). In gastric MALT lymphoma, t(11;18)(q21;q21) was significantly associated with infection by CagA-positive strains of Helicobacter pylori. As CagA-positive strains of H pylori are much more potent in induction of host inflammatory responses, including activation of neutrophils, which release highly genotoxic oxygen reactive species, we therefore examined neutrophil infiltration in recognized precursors of MALT lymphoma including H pylori-associated gastritis, lymphoepithelial sialadenitis, and Hashimoto thyroiditis. Neutrophil infiltration was prominent in H pylori-associated gastritis but not in lymphoepithelial sialadenitis and Hashimoto thyroiditis. Our results demonstrate that t(11;18)(q21; q21) occurs at markedly variable frequencies in MALT lymphoma of different sites and suggest that the occurrence of the translocation is influenced by the nature of premalignant diseases associated with MALT lymphoma. Oxidative damage might play a role in development of t(11;18)(q21; q21).

Adaptor Proteins, Signal Transducing↗
PubMed2003

Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2.

Four Hodgkin's lymphoma cell lines (KM-H2, HDLM-2, L428, L1236) were analyzed for cytogenetic aberrations, applying multiplex fluorescence in situ hybridization, chromosome banding and comparative genomic hybridization. Each line was characterized by a highly heterogeneous pattern of karyotypic changes with a large spectrum of different translocated chromosomes (range 22-57). A recurrent finding in all cell lines was the presence of chromosomal rearrangements of the short arm of chromosome 2 involving the REL oncogene locus. Furthermore, multiple translocated copies of telomeric chromosomal segments were frequently detected. This resulted in a copy number increase of putative oncogenes, e.g., JAK2 (9p24) in 3 cell lines, FGFR3 (4p16) and CCND2 (12p13) in 2 cell lines as well as MYC (8q24) in 1 cell line. Our data confirm previous cytogenetic results from primary Hodgkin's tumors suggesting an important pathogenic role of REL and JAK2 in this disease. In addition, they provide evidence for a novel cytogenetic pathomechanism leading to increased copy numbers of putative oncogenes from terminal chromosomal regions, most probably in the course of chromosomal stabilization by telomeric capture.

Chromosome Aberrations↗
PubMed2003

MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma.

The MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen in 30% of cases of mucosa-associated lymphoid tissue (MALT) lymphoma. Here, we show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma (B-NHL) of various histologic subtypes either through translocation to the immunoglobulin heavy chain (IGH) locus or by genomic amplification. First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;18)(q32;q21), cytogenetically identical to the translocation involving BCL2, were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of both by long-distance inverse polymerase chain reaction showed breakpoints lying 1 to 2 kilobase (kb) centromeric of the first 5' MALT1 exon; both cases showed MALT1 overexpression at either RNA or protein levels. Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques. Using array CGH, 2 peaks of genomic amplification were observed, one centered around BCL2 and the other around MALT1. Ofthe 3 cell lines with MALT1 amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse transcription-polymerase chain reaction (QRT-PCR), and Western blotting. To determine if comparable events occurred in primary MALT and splenic MZL tumors, 40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 overexpression were seen in 2 cases. Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL.

Aged↗
PubMed2003

Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma.

Structural aberrations of the short arm of chromosome 2, mostly resulting in gains of 2p13 approximately 16, have recently been described as being highly recurrent in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). As these gains consistently lead to increased copy numbers of the REL oncogene locus, we investigated the expression of the c-Rel protein in a series of 30 cHL cases with known genomic REL status as determined by comparative genomic hybridization and interphase cytogenetics. Expression of the c-Rel protein was investigated in 26 biopsies by immunohistochemistry. Distinct patterns were observed in HRS cells with no staining, cytoplasmic, and/or nuclear staining for c-Rel. All 13 samples with additional copies of the REL locus displayed nuclear staining for c-Rel, while 13 cHL samples lacking chromosome 2 (2p) gains displayed a significantly lower proportion or complete absence of HRS cells with nuclear c-Rel expression. Detailed analysis using combined immunophenotyping and interphase cytogenetics of individual HRS cells demonstrated that REL gains correlated with the presence of nuclear c-Rel staining. Additionally, in 2 cHL samples with translocation breakpoints in 2p13 approximately 16, nuclear staining of c-Rel was observed; in one of them the staining pattern was indicative of a truncated c-Rel protein. The correlation between structural aberrations involving the REL locus and nuclear c-Rel accumulation in HRS cells qualifies REL as a target gene of the frequent gains in 2p in cHL. The data suggest that REL aberrations are a genetic mechanism contributing to constitutive nuclear factor (NF)-kappa B/Rel activation in cHL.

Cell Line↗
PubMed2003

Identification of candidate tumor-suppressor genes in 6q27 by combined deletion mapping and electronic expression profiling in lymphoid neoplasms.

Deletions in the long arm of chromosome 6 (6q) are among the most frequent chromosome aberrations in lymphoid neoplasms. Recently, the region of minimal deletion (RMD1) in 6q27 was narrowed down to 5-9 Mb. In the present study, we aimed to define the distal border of the commonly lost region in 6q27 more precisely and to identify and investigate tumor-suppressor genes (TSGs) from this region. Twenty-nine cases, in which our previous fluorescence in situ hybridization (FISH) screening that used a set of 36 YAC probes revealed loss in 6q25-27, were further investigated by means of FISH. In all cases, deletions of 6q27 extended from yeast artificial chromosome (YAC) 977e10 spanning the proximal border of RMD1 to the most telomeric YAC 933f7 within the recently established YAC-contig of this region. An interstitial homozygous deletion, flanked by the telomeric probe TelVysion6q and YAC 971g12, was detected, which substantially narrows down the RMD1. To identify candidate TSGs down-regulated in malignant lymphomas from this region of homozygous loss, we performed electronic profiling of expressed sequences mapped to this region. This analysis suggested the gene PDCD2 originally thought to be involved in programmed cell death to be probably down-regulated in malignant B-cell lymphomas compared to normal B lymphocytes. Nevertheless, mutation analyses failed to identify mutations in the coding region of PDCD2 in nine lymphomas with FISH-proved 6q27 deletions. Furthermore, epigenetic studies in these nine and an additional 48 lymphomas did not show altered methylation of the PDCD2 locus in these tumors. Possibly haploinsufficiency is effectual in accelerating tumor progression.

Cell Line, Transformed↗
PubMed2003

Interleukin-1 gene polymorphisms and experimental gingivitis.

BACKGROUND: Recently, an association between the severity of periodontitis and specific variations in the interleukin-1 (IL1) alpha and beta genes has been demonstrated. AIM: : The purpose of this study was to evaluate the relationship of the IL1 genotype to the development of experimental gingivitis. MATERIALS AND METHODS: Twenty young adult subjects presenting with healthy gingival conditions participated after giving their informed consent. The group included 10 risk genotype positive (P+) and 10 risk genotype negative (P-) individuals. The IL1 genotypes were determined on DNA samples from peripheral blood using PCR-RFLP analyses for the IL1alpha and IL1beta polymorphisms. Experimental gingivitis was allowed to develop in two posterior sextants per subject. Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and days 2, 7, 9, 14, 16 and 21. The day 21 results for BOP and GCF as well as the rate of increase of these parameters - mean area under the curve (AUC) and mean increase per day (slope) - were evaluated using risk analyses for IL1 genotype, smoking status and gender. RESULTS: Experimental gingivitis developed with a gradual increase in BOP scores and GCF values (expressed as Periotron units=PU) from baseline to day 21 (BOP, P+: 0.5 to 26.0%; P-: 1.0 to 28.1%; GCF, P+: 36.8 to 138.5 PU, P-: 43.1 to 143.4 PU). No significant risk was associated with P+ and P- for day 21 results, AUC or slope. CONCLUSION: The results of this study failed to provide evidence that the IL1 risk genotype was associated with higher GCF volume and percentage BOP during the development of experimental gingivitis.

Adult↗
PubMed2003

Common clonal T-cell origin in a patient with T-prolymphocytic leukaemia and associated cutaneous T-cell lymphomas.

An unusual course was observed in a patient with indolent T-prolymphocytic leukaemia (T-PLL) who subsequently developed mycosis fungoides (Mf), lymphomatoid papulosis (LyP) and cutaneous CD30+ anaplastic large cell lymphoma (ALCL). Polymerase chain reaction analysis demonstrated identical monoclonal T-cell receptor-beta and -gamma gene rearrangements in all the different clinical entities. Furthermore, cytogenetic studies revealed the same aberrant clone with trisomy of chromosome 8 in T-PLL and ALCL cells. This unique observation suggests that in T-PLL, the leukaemic cells might undergo secondary transformation, subsequently resulting in different phenotypes of cutaneous T-cell lymphoma.

Aged↗
PubMed2003

Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes.

The clinical and pathological features, including karyotype data and BCL2 protein expression pattern, of follicular lymphoma without a t(14;18)(q32;q21) have not been well defined. We have identified and conducted a detailed analysis of 50 cases with follicular lymphoma who lack the t(14;18). Fluorescent in situ hybridization (FISH) analysis was used to exclude cases with a cryptic IGH/BCL2 rearrangement. BCL2 protein expression level was assessed by immunohistochemistry. The karyotypes were assessed for recurrent sites of structural rearrangement, duplications and deletions on a band-by-band basis, and compared with a large cohort of cases with t(14;18). A distinct pattern of chromosomal alterations was identified in the cases without t(14;18). BCL2 protein overexpression was detected in 33% of 49 tested cases. In this minority, the karyotypes frequently showed increased copies of chromosome 18. The majority of cases (67%) did not show BCL2 overexpression and were characterized prominently by the presence of t(3;14)(q27;q32), implying a role for BCL6. Follicular lymphomas that lack a t(14;18) were segregated into two subgroups with distinct cytogenetic, phenotypic and possibly clinical features: one with BCL2 protein overexpression not related to an IGH/BCL2 rearrangement and a second without BCL2 overexpression. Objective identification of BCL2 expression level as well as BCL2 and BCL6 status by cytogenetic or FISH analysis has potential clinical utility and may yield insights into alternative genetic mechanisms associated with B-cell lymphomas with a follicular growth pattern.

Adult↗
PubMed2003

Autosomal dominant lateral temporal epilepsy: clinical spectrum, new epitempin mutations, and genetic heterogeneity in seven European families.

PURPOSE: [corrected] To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE). METHODS: A personal and family history was obtained from each affected and unaffected member, along with a physical and neurologic examination. Routine and sleep EEGs, computed tomography (CT), or magnetic resonance imaging (MRI) were performed in almost all the patients. DNAs from family members were typed with several microsatellite markers localized on either side of LGI1 at 10q24 and screened for LGI1 mutations. RESULTS: The seven families included a total of 34 affected individuals (10 deceased). The age at onset ranged between 8 and 50 years (average, 22 years). Twenty-six patients had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Less frequent ictal symptoms were visual, psychic, or aphasic seizures, the latter occurring in isolation in one family. The attacks were rare and well controlled by antiepileptic drug treatment but recurred after drug discontinuation. Interictal EEGs were usually unrevealing. MRI or CT scans were negative. Analysis of LGI1/Epitempin exons failed to show mutations in three pedigrees. Linkage analysis strongly suggested exclusion of linkage in one of these families. We found two novel missense mutations, a T-->C substitution in exon 6 at position 598, and a T-->A transition in exon 8 at position 1295, the latter being detected in a family with aphasic seizures. CONCLUSIONS: Our data confirm the inclusion of aphasic seizures within the ADLTE clinical spectrum, suggest the existence of locus heterogeneity in ADLTE, and provide new familial cases with LGI1 missense mutations associated with the disease.

Adolescent↗
PubMed2003

Genomic abnormalities acquired in the blastic transformation of splenic marginal zone B-cell lymphoma.

Among 20 cases of typical splenic marginal zone lymphoma (SMZL), two cases had blastic transformation. The genetic mechanisms underlying the morphologic transformation were investigated by comparing genetic changes in initial and blastic phases. A complex karyotype including trisomy of 3q and genomic gain of 17q22-q24 was seen in both cases at diagnosis. However, the extra copy of 3q was lost during the transformation process in both tumors. Additionally, the Karpas 1718 cell line, which was derived from a patient with transformed SMZL and carried a trisomy of 3q, also evidenced the spontaneous loss of the extra 3q during the culturing process. Other acquired abnormalities observed exclusively in the transformation phase included amplification and/or translocation of bands 7p22-q22 and 19p13. These findings suggest that the loss of + 3q and the acquisition of other genomic imbalances may represent unique markers for the transformation process of SMZL. We hypothesize that the trisomy of 3q may correlate with the indolent nature of SMZL, and that the loss of this acquired abnormality leads to or accompanies the development of blastic tumors.

Blast Crisis↗