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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young male patient progressed rapidly from localized abdominal lymph node enlargement to overt acute lymphoblastic leukemia. Despite aggressive treatment, he died of progressive CNS leukemia 5 months after initial presentation. At diagnosis, karyotypic analysis of an abdominal lymph node revealed the coexistence of t(14;18) (q32;q21), specific for follicular lymphoma, and t(8;22) (q24;q11), a variant Burkitt translocation. Such cases might be considered as a model for a general mechanism of tumor progression with cascade-like involvement of oncogenes.
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PMID:Simultaneous occurrence of t(14;18) and t(8;22) common acute lymphoblastic leukemia. 155 91

The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.
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PMID:Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. 188 22

About half of the patients with follicular lymphoma will develop an aggressive B cell lymphoma with morphological changes in growth pattern and cellular morphology. Changes of the immunophenotype, especially of the expression of immunoglobulin (Ig) have been documented less frequently. Multiple tumor samples of two patients with follicular lymphoma who developed tumor progression, were studied by Southern blot analysis for rearrangements of the Ig genes and the oncogenes BCL2 and MYC. In both patients, the general pattern of Ig gene rearrangements, especially of the Ig light-chain genes, and the structure of the t(14;18) breakpoint as assessed by the polymerase chain reaction (PRC) and fine restriction mapping, remained unaltered with time. However, both within the functional Ig heavy-chain allele and around the t(14;18) breakpoint, extensive secondary alterations took place. This indicates clonal evolution rather than the appearance of an independent lymphoma. In the first case with progression from follicular lymphoma to Burkitt's lymphoma 3 years after diagnosis, alterations were especially present 3' of the t(14;18) breakpoint. In the second patient with a change from follicular to diffuse centroblastic lymphoma 4 years after diagnosis, subsequent class switches from IgM to IgG and to defective IgH expression were accompanied by deletion of C mu sequences and a rearrangement of the MYC gene, respectively. Additionally, in both patients alterations in individual restriction sites occurred, which most likely were due to somatic mutations within both the functional IgH and translocated allele. Our data indicate that complex alterations of both the functional and non-functional IgH allele may accompany tumor progression and may erroneously suggest the appearance of independent clones by Southern blot analysis. It remains to be established whether these alterations are causative events or the consequence of genetic instability and clonal evolution.
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PMID:Histological conversion of follicular lymphoma with structural alterations of t(14;18) and immunoglobin genes. 756 20

We report overexpression of the proto-oncogene bcl-2 in gastrointestinal adenocarcinoma and its precursor lesions. The bcl-2 proto-oncogene is centrally involved in the oncogenesis of human follicular lymphoma via a chromosomal translocation t(14;18)(q32;q21) and is also expressed in the epithelial regenerative compartment or the basal crypts of the normal colon and small intestine. We describe an immunohistochemical analysis of fixed, paraffin-embedded tissue using both a polyclonal rabbit and a monoclonal mouse antibody to the Bcl-2 protein. In addition to confirming bcl-2 expression in normal colonic and small intestinal crypts, we also observed expression in the gastric epithelial regenerative compartment, the mucous neck region. No increased expression was found in nonneoplastic or inflammatory gastrointestinal conditions, including ulcerative colitis, Crohn's disease, or inflammatory or hamartomatous polyps. Increased bcl-2 expression, however, was present in hyperplastic colonic polyps and in the majority of dysplastic lesions, from the earliest precursors through large adenomas, high grade flat dysplasia, and adenocarcinoma, all in comparison with adjacent internal control normal epithelium. Increased expression was present in dysplastic glandular lesions from all gastrointestinal sites, including colon, small bowel, and stomach. Furthermore, bcl-2 expression was frequently abnormal in nondysplastic epithelium surrounding dysplastic lesions, suggesting that altered expression occurred before the development of morphological dysplasia. Specifically, directly contiguous morphologically nondysplastic epithelium often showed abnormal bcl-2 expression throughout the full length of the crypt-villus axis. This expression pattern gradually diminished to involve only the crypt base (the normal pattern of expression), proceeding away from malignant or dysplastic lesions. Abnormal bcl-2 immunoreactivity in 1), the earliest precursor dysplastic lesions and its persistence throughout neoplastic progression and 2), contiguous morphologically unaltered nondysplastic epithelium suggests that bcl-2 alterations occur early during the morphological and molecular sequence of events leading to gastrointestinal epithelial neoplasia.
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PMID:The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. 785 28

The t(14;18)(q32;q21) chromosomal translocation is observed in more than 75% of cases of follicular lymphoma. Several additional chromosomal abnormalities, which might contribute to tumor progression, have also been described. However, prognostic implications of cytogenetic features in follicular lymphoma have not been clearly established. In an attempt to correlate cytogenetic findings with clinical outcome, we have studied survival and risk of transformation into a more aggressive lymphoma in 66 follicular lymphoma patients from whom a lymph node had been karyotyped at the time of diagnosis. A t(14;18) was the most common abnormality, having been observed in 51 patients (77%), but this showed no correlation with clinical outcome. Seventeen other recurrent numerical or structural abnormalities were identified in more than 10% of the patients. A high percentage of cells (> or = 90%) with abnormal metaphases and a number of chromosomal breaks higher than 6 were associated with a poor survival (P > .01 each). Patients with an abnormality of chromosome region 1p21-22 (P < .01), of 6q23-26 (P < .001), or of the short arm of chromosome 17 (P < .001) had a significantly shorter survival in univariate analysis. Multivariate analysis identified a break at 6q23-26 (P = .01) and 17p (P = .01) as independent prognostic factors in this population. The risk of transformation into a diffuse large-cell lymphoma was significantly higher in patients with either a 6q23-26 (P < .001) or a 17p (P < .01) abnormality. Chromosomal analysis of follicular lymphoma at the time of diagnosis can thus provide important information about the risk of transformation and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic value of chromosomal abnormalities in follicular lymphoma. 804 24

The bcl-2 proto-oncogene encodes a protein that blocks programmed cell death (apoptosis). Although bcl-2 has been shown to be involved in the development of follicular lymphoma via a chromosomal translocation t(14;18), little is known about its function in non-hematolymphoid neoplasms. The bcl-2 protein is normally expressed in the regenerative crypt compartment of the colon, small intestine, and stomach, and has been found to be abnormally overexpressed as an early event in the dysplasia-carcinoma sequences of both ulcerative colitis-related and gastric neoplasias. This study was undertaken to evaluate the role of bcl-2 in the Barrett's metaplasia-dysplasia-carcinoma sequence. Thirty-six esophageal resection specimens were studied, using a monoclonal antibody to the bcl-2 protein on fixed paraffin-embedded specimens. Barrett's mucosa was present in each specimen: low-grade dysplasia in 35, high-grade dysplasia in 34, intramucosal carcinoma (IMC) in 23, and submucosal carcinoma in 13. In addition, a section of the gastric resection margin was evaluated for bcl-2 immunoreactivity in each case. In all cases, the regenerative compartment of the gastric mucosa in the resection margins stained for bcl-2; however, no immunoreactivity was seen in any of the cases of Barrett's mucosa with or without dysplasia or carcinoma. We conclude that, in contrast to its role in gastric neoplasia, bcl-2 alterations are not an important molecular marker in the neoplastic progression of Barrett's mucosa.
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PMID:bcl-2 protein expression in the Barrett's metaplasia-dysplasia-carcinoma sequence. 855 77

The proto-oncogene bcl-2 is associated with follicular lymphoma involving translocation t(14;18)(q32;q21) and is also overexpressed in various neoplasms. We report deregulation of bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein in formalin-fixed paraffin-embedded tissue sections revealed that severe epithelial dysplasias had a higher percentage of immunoreactivity than did mild and moderate dysplasias and squamous cell carcinomas. Expression of this oncoprotein was directly proportional to the degree of epithelial dysplasia, and nondysplastic basal cells contiguous to neoplastic lesions also expressed bcl-2. These findings, along with down-regulation of bcl-2 in differentiating carcinomas, suggest a role for this oncoprotein in relatively early stages of oral tumor progression. Differentiating neoplastic cells with marginal or no bcl-2 reactivity showed heterogeneous cell labeling of varying intensity for differentiation-associated cytokeratin (CK13), indicating their inverse topographic relationship.
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PMID:Immunohistochemical evaluation of bcl-2 oncoprotein in oral dysplasia and carcinoma. 963 3

The study of chromosomal changes related to tumor progression in NHL is complicated by the various histologic classification systems and the lack of large serial studies comparing abnormalities at different disease stages. The T-cell lymphomas frequently involve rearrangements of the T-cell receptors and tumor progression is marked by a change from single cell aberrations and polyclonality in low grade disease to monoclonal formation, complex clones, polyploidy, and abnormalities of 1p, 6q, 7, and 13 in high grade T-NHL. In B-cell NHL, specific translocations and oncogene rearrangements are associated with specific NHL subtypes de novo; many of these translocations involve immunoglobulin genes, such as t(14;18) in follicular lymphoma, t(11;14) in MCL, t(3;14) in DLLC, and t(8;14) in Burkitt's lymphoma. Tumor progression is associated with secondary abnormalities which are generally not confined to a particular NHL subtype. Some abnormalities, such as those involving chromosomes 1, 6, and 17, >4-6 clonal markers/cell, and rearrangements of c-MYC and TP53, have prognostic significance while others, such as trisomies 7, 12, 18, and X, are associated with tumor progression but their influence on overall survival is uncertain.
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PMID:Cytogenetic changes in the progression of lymphoma. 972 Jul 11

Little is known about stepwise deregulation of specific genes leading to lymphoid malignancy. Aberrant myc gene expression in transgenic mice is correlated with B cell lymphomagenesis. We generated a unique transgenic mouse model in which deregulated murine E mu-N-myc transgene expression leads to development of indolent B cell lymphoma. Tumor cells were monoclonal, morphologically mature and surface immunoglobulin expressing B cells. Tumors arose in a disease course and exhibited a cytoarchitectural appearance reminiscent of human follicular lymphoma. Yet tumor cells were staged as preB since they failed to rearrange the immunoglobulin light chain genes. Retroviral insertion mutagenesis analyses of adult transgenic mice infected as newborns with murine leukemia virus revealed decreased disease latency, increased lymphoma incidence and a histologically more mature tumor type. Proviral insertion sites were not equivalent when accelerated E mu-N-myc indolent lymphomas were compared to accelerated c-myc preB cell lymphomas. The bcl-2 gene was not disrupted in either spontaneous or provirally accelerated E mu-N-myc lymphomas. These findings suggest that tumor progression in N-myc-associated indolent B cell lymphoma can proceed along diverse pathways involving distinctly different combinations of deregulated and/or intact genes than those pathways described in highly aggressive forms of myc-related murine preB cell disease.
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PMID:Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors. 979 78

Rearrangement of chromosomal bands 1q21-23 is one of the most frequent chromosomal aberrations observed in hematological malignancy. The genes affected by these rearrangements remain poorly characterized. Typically, 1q21-23 rearrangements arise during tumor evolution and accompany disease-specific chromosomal rearrangements such as t(14;18) (BCL2) and t(8;14) (MYC), where they are thus thought to play an important role in tumor progression. The pathogenetic basis of this 1q21-23-associated disease progression is currently unknown. In this setting, we surveyed our series of follicular lymphoma for evidence of recurring 1q21-23 breaks and identified three cases in which a t(14;18)(q32;q21) was accompanied by a novel balanced t(1;22)(q22;q11). Molecular cloning of the t(1;22) in a cell line (B593) derived from one of these cases and detailed fluorescent in situ hybridization mapping in the two remaining cases identified the FCGR2B gene, which encodes the immunoreceptor tyrosine-based inhibition motif-bearing IgG Fc receptor, FcgammaRIIB, as the target gene of the t(1;22)(q22;q11). We demonstrate deregulation of FCGR2B leading to hyperexpression of FcgammaRIIb2 as the principal consequence of the t(1;22). This is evidence that IgG Fc receptors can be targets for deregulation through chromosomal translocation in lymphoma. It suggests that dysregulation of FCGR2B may play a role in tumor progression in follicular lymphoma.
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PMID:The IgG Fc receptor, FcgammaRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma. 1061 14


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