Biomedical subjects

S C Jhanwar

Publications and source records attributed to S C Jhanwar.

At least 55 records · Page 3Linked to original sources

PubMed1995

Molecular diagnosis of synovial sarcoma and characterization of a variant SYT-SSX2 fusion transcript.

The translocation t(X;18)(p11;q11) is seen in > 80% of synovial sarcomas (SS) with informative karyotypes. The breakpoints of the t(X;18) have been cloned and shown to involve two novel genes, SSX (at Xp11) and SYT (at 18q11), which produce a chimeric SYT-SSX transcript as a result of the translocation. Recently, SSX has been shown to be duplicated, with both copies, SSX1 and SSX2, located within distinct subregions of Xp11. We performed a reverse transcriptase polymerase chain reaction (RT-PCR) assay for both chimeric SYT-SSX transcripts in a series of 35 SS (29 monophasic, 6 biphasic) to assess its usefulness in molecular diagnosis and to evaluate the incidence of molecular variants. Of the 35 cases, 29 (83%) showed a specific SYT-SSX RT-PCR product, using a consensus primer for SSX1 and SSX2 Upon excluding three negative cases that had poor quality RNA, the proportion of positives rose to 91% (29/32). The 29 positive cases were further studied using primers specific for either SSX1 or SSX2; 19 cases were positive for SYT-SSX1 and 10 for SYT-SSX2. The relationship of histological subtype (monophasic versus biphasic) to SSX1 or SSX2 involvement was not statistically significant. In a single histologically unremarkable monophasic SS, a slightly larger SYT-SSX2 RT-PCR product was observed. Sequencing of this novel variant showed a 129-bp segment inserted between the usual SYT and SSX2 fusion points, of which 126 bp were derived from a more proximal (5') portion of SSX2 The 3 bp immediately 5' to the fusion point could not be assigned to either SYT or SSX2 and may represent an insertion-deletion or a cryptic splicing event. This fragment maintains the reading frame of the chimeric product and encodes a predicted protein larger by 43 amino acids, which nevertheless replaces the region homologous to the transcriptional repression domain Kruppel-associated box, recently recognized in the 5' portion of the SSX genes, with all but the 3' end of the SYT transcript. Thus, a diagnosis of SS may be confirmed in > 90% of cases using RT-PCR detection of the chimeric transcript resulting from the t(X;18), and the incidence of molecular variants appears low.

Adolescent↗

PubMed1994

p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma.

To determine whether p16 is altered in human malignant mesothelioma (MM), molecular analysis of multiple 9p loci was performed on 40 cell lines and 23 primary tumors from 42 MM patients. We identified homozygous deletions of p16 in 34 (85%) cell lines and a point mutation in 1 line. Down-regulation of p16 was observed in 4 of the remaining cell lines, 1 of which displayed a DNA rearrangement of p16. Homozygous deletions of p16 were identified in 5 of 23 (22%) primary tumors; no mutations or rearrangements were found in these specimens. Four cell lines displayed a single homozygous deletion proximal to or distal to p16; 4 others had 2 nonoverlapping deletions, one involving p16 and the other involving a region proximal to this locus. These data indicate that alterations of p16 are a common occurrence in MM cell lines and, to a lesser extent, in primary tumors. Furthermore, deletions of 9p21-p22 outside of the p16 locus may reflect the involvement of other putative tumor suppressor genes that could also contribute to the pathogenesis of some MMs.

Base Sequence↗

PubMed1994

Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma.

Previous cytogenetic investigations have revealed frequent deletions and other unbalanced structural rearrangements of 3p in human malignant mesothelioma. We have performed a restriction fragment length polymorphism analysis by using the polymerase chain reaction and primer sets for seven DNA markers to examine loss of heterozygosity (LOH) from 3p in 25 malignant mesotheliomas. Among 24 cases informative at one or more 3p loci, 15 (62.5%) exhibited LOH with at least one marker. Deletion mapping in these tumors indicates that the common region of chromosomal loss resides within band 3p21, in the vicinity of the D3F15S2 locus. These results suggest that allelic loss from 3p21 is a frequent occurrence in malignant mesothelioma and that one or more putative tumor suppressor genes at this site contribute to the pathogenesis of this malignancy.

Alleles↗

PubMed1994

Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST).

Malignant peripheral nerve sheath tumors (MPNST) are known to develop in patients with neurofibromatosis 1 (NF1), thus providing an excellent model for the study of multistep carcinogenesis in genetically predisposed individuals. To determine the sites of gene(s) involved in such a process, we have performed cytogenetic analysis on 10 tumors. The patients were five males and five females ranging in age from 15 to 77 years. Nine patients had NF1. Karyotypic analysis of these tumors exhibited complex clonal abnormalities of several chromosomes. Recurrent abnormalities (numerical as well as structural) of chromosomes 1, 11, 12, 14, 17, and 22 occurred in a substantial proportion of tumors studied. Although abnormalities of these chromosomes have been seen in a variety of other tumors, the aberrations of chromosomes 17 and 22 are of particular interest; chromosomes 17 and 22 carry the genes for NF1 and NF2, respectively. In addition to other clonal aberrations, six tumors had abnormalities of both chromosomes 17 and 22, while three tumors only had an abnormality of chromosome 17. In eight tumors a structural abnormality of chromosome 17 included deletion or a relative deficiency of 17p; in four of the tumors there was also either deletion or rearrangement of the NF1 locus at the cytogenetic level. One tumor had monosomy of chromosome 17. The abnormality of chromosome 22 was deletion of 22q11.2-->qter. This study suggests that the germline mutation in one of the copies accompanied by loss or inactivation of the second copy of the NF1 gene and tumor suppressor gene(s) on 17p and 22q may be associated with the neoplastic transformation; abnormalities of other chromosomes may be related to progression of MPNST. Although the role of the p53 gene in carcinogenesis is well documented in several tumor types, the role of the NF2 gene or other unidentified tumor suppressor gene(s) on chromosomes 22q, 1p, 11, 12, 14 remains to be seen.

Adolescent↗

PubMed1994

Analysis of nuclear and mitochondrial DNA alterations in thyroid and renal oncocytic tumors.

The search for mitochondrial DNA (mtDNA) defects in oncocytic neoplasms has been the subject of several recent studies. We have performed qualitative and quantitative analysis of nuclear and mitochondrial DNAs in a series of 19 renal and 12 thyroid oncocytic tumors to identify specific alterations that might predict the clinical and biological behavior of these tumors. Allelic losses were seen in 2 of 19 renal tumors and 5 of 12 thyroid tumors. Among all loci (3p, 3q, 9q, 10q, 11p, 17p, and 17q) that showed losses, losses at 10q (one renal tumor and three thyroid tumors) were significantly higher (P < 0.05) than expected. Analysis of the COX I region previously reported to be altered in oncocytomas and the delta-loop region of mtDNA showed no detectable abnormalities in the restriction pattern in 10 renal and five thyroid tumors. PCR analysis of the commonly deleted 4,977-bp region failed to detect an increased frequency of mtDNA deletions in tumors compared to the controls. In addition, segmental amplification of the complete mtDNA from a renal oncocytoma using nine sets of primers revealed no gross alteration in mtDNA. Oncocytic tumors showed a mean 5-fold increase in mitochondrial DNA, which was significant (P < 0.001) when compared to corresponding controls. The relative increase in the cellular content of mtDNA may be associated with alterations in the normal coordinated interaction between the nuclear and mitochondrial genomes. Allelic deletions at 10q may be significant in the biology of oncocytic tumors, and their impact on the clinical behavior of these tumors warrants further investigation.

Base Sequence↗

PubMed1993

Allelic deletions in renal tumors: histopathological correlations.

Allelic loss on the short arm of chromosome 3 (3p) is considered to be one of the early detectable events in the pathogenesis of renal cell carcinoma (RCC). Conflicting reports, however, suggest that this event may be absent in some renal tumors. The present study attempts to further define subgroups of renal tumors associated with 3p deletions. In addition, we have also attempted to identify late genetic events associated with tumorigenesis and tumor progression. Eighty-two primary renal tumors (69 RCC and 13 oncocytic tumors) were analyzed by restriction fragment length polymorphism analysis directed at chromosomes 3, 11p, 17p, and 18q. Results were correlated with histopathological information. Deletions of 3p were seen in nonpapillary RCC of all cell types, but were absent in oncocytic and most papillary tumors. Among the 60 nonpapillary RCC, significant correlations were seen between deletion of 17p and tumor grade (P = 0.037), P stage (P = 0.027), and nodal metastases (P = 0.042). We therefore conclude that 3p deletions, although not specific to any cell type or histological pattern of RCC, are seen in a majority of clear cell nonpapillary RCC but are absent in oncocytic and most papillary tumors. Additional allelic losses on chromosome 17p are associated with advanced disease and, therefore, may be related to tumor progression. Further studies on larger series of patients with extended follow-up will be necessary to investigate the prognostic value of molecular genetic markers in RCC.

Alleles↗

PubMed1993

Homozygous deletions within 9p21-p22 identify a small critical region of chromosomal loss in human malignant mesotheliomas.

Previous DNA analyses have demonstrated that 9p13-p22 is a frequent site of chromosomal loss in leukemia, glioma, melanoma, and lung and bladder carcinomas. Recent cytogenetic studies have revealed recurrent alterations of 9p in malignant mesothelioma (MM). We have performed gene dosage studies of 23 MM cell lines, using probes for several 9p21-p22 loci (IFNB, IFNA/IFNW, D9S3, D9S126, D9S169, and D9S171), to identify a common region of deletion. Homozygous and/or hemizygous deletions were identified in 19 (83%) cell lines. Homozygous losses (10 cell lines; 43%) occurred most often at the D9S171 and IFNA/IFNW loci. In 8 cell lines, 2 or more of the 9p loci examined were found to be homozygously lost; 2 others displayed homozygous losses only at the D9S171 locus. Results from our deletion mapping analysis suggest that D9S171 is located between IFNA/IFNW and D9S126. The data presented here indicate that allelic loss from 9p21-p22 is a common occurrence in MM and further delineate the location of a putative 9p tumor suppressor gene(s) to a region between IFNA/IFNW and D9S171. These MM cell lines may facilitate efforts to define an even smaller critically deleted region, leading to the eventual cloning and characterization of this gene.

Base Sequence↗

PubMed1993

6q deletions define distinct clinico-pathologic subsets of non-Hodgkin's lymphoma.

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate-grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.

Biopsy↗

PubMed1993

Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma.

Detailed cytogenetic analyses were carried out on primary tumor specimens and cell lines from 23 patients with pleural malignant mesothelioma (MM). Clonal abnormalities were identified in 20 of 23 MM. In 3 cases, karyotypic data were compiled from harvests of both short-term cultures (1-3 days), and primary cultures grown on murine feeder layers for several weeks. The karyotypes obtained with these 2 different culture methods were very similar, although polyploid versions of abnormal clones were found only in the long-term cultures. In addition, while short-term cultures from 9 tumor biopsies usually exhibited near-diploid clones, cell lines derived from 11 tumors tended to have higher ploidies. Each of the cytogenetically abnormal MM displayed multiple clonal alterations. The 2 most frequent changes were chromosomal losses of specific regions in 1p (17 cases) and 9p (16 cases). The shortest regions of overlap of these losses were at 1p21-p22 and 9p21-p22, respectively. Other common abnormalities included losses of 3p21 (13 cases) and 6q15-q21 (9 cases), and numerical losses of chromosomes 14, 16, 18, and 22 (each observed in 10-13 tumors). In many of the MM examined, most or all of these recurrent changes occurred in combination, suggesting the involvement of a pathogenetic cascade in this cancer. The pattern of recurrent chromosomal losses suggests that these regions represent the locations of tumor suppressor genes whose loss/inactivation may have a pivotal role in MM tumorigenesis.

Adult↗

PubMed1993

MDM2 gene amplification in metastatic osteosarcoma.

The human homologue of the murine double minute 2 gene (MDM2), a p53-binding protein which may act as a regulator of p53 protein function, has recently been cloned. Initial studies of this gene in a variety of human tumors have shown frequent gene amplification in most types of sarcomas, including osteosarcomas. Amplification of the MDM2 gene may produce a functional inactivation of the p53 protein. To examine possible clinical or pathological correlates of MDM2 gene amplification in osteosarcoma, we studied 28 specimens on 26 patients with high grade osteosarcoma (16 primary, 11 metastatic, and 1 local recurrence) for MDM2 gene amplification by Southern blot analysis, using two MDM2 complementary DNA probes isolated by polymerase chain reaction. Four specimens (14%) showed amplification, including 3 metastases and 1 local recurrence. None of the primary osteosarcoma specimens had detectable MDM2 gene amplification. None of the specimens tested showed MDM2 gene rearrangement. In the present series, MDM2 gene amplification was detected significantly more frequently in metastatic or recurrent osteosarcomas than it was in primary osteosarcomas (P = 0.02). Our data suggest that MDM2 gene amplification may be associated with tumor progression and metastasis in osteosarcoma. Further investigation is warranted on the potential clinicopathological correlates of MDM2 gene amplification in osteosarcoma.

Adolescent↗

PubMed1993

Clusters of chromosome 9 aberrations are associated with clinico-pathologic subsets of non-Hodgkin's lymphoma.

In this study we analyzed nonrandom aberrations affecting chromosome 9 in a series of 426 consecutively ascertained, karyotypically abnormal non-Hodgkin's lymphoma (NHL) tumors derived from 407 patients. Cytogenetic abnormalities were correlated with clinical, histologic, and immunologic features. Structural abnormalities of chromosome 9 were identified in 60 specimens derived from 59 patients. The recurring abnormalities among these were associated with 4 clinico-pathologic subsets. The first comprised 7 cases of t(9;14)(p13;q32), 6 of which had small lymphocytic lymphoma, plasmacytoid subtype, and an indolent clinical course. The second group included 12 cases with breaks at 9q11-13 and diffuse lymphomas with a large-cell component and a typical response to combination chemotherapy. The third group was comprised of 7 cases with 9q deletions, with a common deleted region encompassing 9q31-32. These cases were characterized by diffuse B-cell histology, young age, and poor clinical outcome. The fourth subset included 5 intermediate- to high-grade T-cell tumors with breaks at 9q34. This analysis of chromosome 9 aberrations in NHL comprises the first such effort based on a large series of tumors. We identify and report here new clinico-pathologic subsets with shared abnormalities of chromosome 9, which should facilitate new approaches to the analysis of the etiology and clinical behavior of NHL.

Biopsy↗

PubMed1993

Characterization of 9q;15q whole-arm translocation derivatives in non-small cell lung carcinomas by fluorescence in situ hybridization.

We report derivative chromosomes, originally interpreted as 9q;15q whole-arm translocations, in tumor cells from two patients with non-small cell lung cancer (NSCLC). One of the tumors was diagnosed as an adenocarcinoma and the other as an adenosquamous carcinoma. In each case, there was no normal chromosome 9. Because of the pericentromeric location of the breakpoints, classical cytogenetic banding techniques did not permit determination of the centromeric origin of these derivative chromosomes. Fluorescence in situ hybridization (FISH) with satellite (alpha, beta, classical), ribosomal DNA, alpha-interferon (alpha-IFN), and whole chromosome painting probes indicated that the 9;15 rearrangement is dicentric in both tumors. In one of these cases, the derivative chromosome is interpreted as a dic(9;15) (p11;p11.2); the other case has a more complicated rearrangement involving reorientation of pericentromeric sequences. A 9q;15q whole-arm derivative chromosome was reported previously in another lung adenocarcinoma, suggesting that this abnormality may represent a recurrent change in lung carcinomas, particularly those displaying adenomatous features.

Aged↗

PubMed1993

EWS rearrangement in Ewing's sarcoma and peripheral neuroectodermal tumor. Molecular detection and correlation with cytogenetic analysis and MIC2 expression.

The translocation t(11;22)(q24;q12) can be identified in its classical or variant form in approximately 90% of cases of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET). In this tumor group in which the histopathologic diagnosis is often one of exclusion, the cytogenetic demonstration of this translocation has become an invaluable positive diagnostic marker. With the recent cloning of the breakpoint regions of the t(11;22), molecular genetic approaches to the detection of this translocation have become possible. By Southern blotting, the position of the breakpoints on chromosome 22 has been found to be tightly clustered within a 7-kilobase (kb) fragment of the genomic DNA, within a gene designated EWS. In the present study, we examined the efficacy of an EWS complementary DNA (cDNA) probe in detecting the t(11;22) in Southern blots of EcoRI- or HindIII-digested DNA extracted from cases of ES and PNET. We also compared the results of the molecular and cytogenetic analysis with the expression of the ES cell surface antigen MIC2, as demonstrated by immunoperoxidase staining with the monoclonal antibodies O13 and HBA71. Twenty-three specimens were studied, including 18 ES and five PNET. Of 16 cases with clonally abnormal karyotypes, 14 (88%) showed a typical or variant t(11;22). Rearrangements were demonstrated within the EWS gene with the EWS cDNA probe in 20 of 23 specimens (87%), including all of the 14 cases, as well as in one case that displayed clonal numerical chromosome abnormalities only. The MIC2 antigen was expressed in 19 of 20 cases (95%), including all three cases lacking EWS rearrangement.(ABSTRACT TRUNCATED AT 250 WORDS)

12E7 Antigen↗

PubMed1993

Sporadic amplification of the MYC gene in human osteosarcomas.

The MYC proto-oncogene has been shown to be overexpressed in several types of sarcomas, including some osteosarcomas. In most cases, the overexpression is due to gene amplification. The total number of osteosarcoma patients studied, however, remains too small to derive any conclusions regarding the true prevalence and the possible clinical significance of MYC gene amplification. To address the issue more thoroughly, we studied 27 specimens from 25 patients with high-grade osteosarcoma (16 primary, 11 metastatic; 11 adult, 14 pediatric) for MYC gene alterations by Southern blot analysis. Two of 27 specimens (7%) showed MYC gene amplification: a primary fibrohistiocytic osteosarcoma of the femur in a 37-year-old man showed threefold amplification, and a primary Paget's osteosarcoma of the tibia in a 60-year-old man showed fourfold amplification. None of the specimens tested showed MYC gene rearrangement (zero of 27) or activating point mutations at the PvuII site in MYC exon-1 (zero of 26). Hence, the MYC gene is amplified in a subset of osteosarcomas. The possible clinical or biological significance of MYC gene amplification in osteosarcoma may warrant further investigation.

Adult↗

PubMed1992

t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation.

In this series of 426 consecutively ascertained, karyotypically abnormal non-Hodgkin's lymphomas (NHLs) derived from 407 patients, a t(9;14)(p13;q32) was encountered in 7 cases; an additional case demonstrated t(9;14)(p1?3;q32). At the time of detection of t(9;14), four cases were small lymphocytic lymphomas with plasmacytoid features; in three of these the t(9;14) was the sole karyotypic abnormality. In two cases of large-cell NHL demonstrating t(9;14), retrospective review of prior lymph node biopsies showed the presence of a small lymphocytic lymphoma of the plasmacytoid subtype. The remaining two cases comprised a large-cell lymphoma of the brain and a follicular NHL. Thus, six of eight cases (75%) had an initial identical low-grade histology. Immunohistochemical analysis of six cases showed no reactivity with CD1, CD2, CD4, CD5, CD8, and CD10 and high reactivity with CD19 and CD20. All four lymphocytic lymphomas and one of the two large-cell NHLs showed cytoplasmic Ig, consistent with plasmacytoid differentiation. Of the eight cases in this series, six presented with or developed stage IV disease; all were characterized by a 6-month to 5-year clinical phase of indolent disease before treatment was instituted. All five patients with low-grade NHL at the time of cytogenetic analysis were alive with recurrent disease at 3-year median follow-up. The remaining three patients with large-cell diffuse histologies relapsed after intensive therapy and expired at a median of 3 years from diagnosis; two of these showed previous or metachronous small lymphocytic tumors. These results suggest a novel biologically distinct subset of NHL; a neoplasm of mature B lymphocytes with plasmacytoid differentiation, characterized by t(9;14); and an indolent presentation followed by gradual clinical progression of disease.

Adult↗

PubMed1992

Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization.

Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.

Adolescent↗

PubMed1992

Follicular lymphoma with t(8;14)(q24;q32): a distinct clinical and molecular subset of t(8;14)-bearing lymphomas.

The presence of the translocation t(8;14)(q24;q32) has not been well described in follicular lymphoma (FL). In a consecutive series of 278 karyotypically abnormal non-Hodgkin's lymphomas (NHL), six patients with FL showing a t(8;14) without a t(14;18)(q32;q21) were identified. They ranged in age from 45 to 73 years. The cell type was mixed in four patients, small-cleaved in one, and large-cleaved in one; four cases also contained diffuse areas. All cases tested displayed monoclonal surface Ig. The clinical courses were consistent with the histologic subtypes, being less aggressive than other t(8;14)-bearing NHL. In five cases, frozen tissue was available for Southern blotting. The BCL2 gene showed a germline configuration when studied with the MBR, MCR, and 5' cDNA probes. The MYC gene also appeared unrearranged using an exon-1 probe with EcoRI or HindIII digestion. Analysis of the Ig heavy chain (IgH) gene with a JH region probe and BamHI or EcoRI digestion showed only one rearranged band in all cases, indicating that the 14q32 breakpoint did not lie in either the J or switch-mu (SM) regions. In four cases, the exon-1/intron-1 border of the MYC gene, a target area for point mutations in cases of t(8;14) that do not display rearrangements of the MYC gene, was enzymatically amplified and sequenced; no point mutations were identified. The indolent behavior of our six cases, and the finding that the molecular structure of the t(8;14) in these cases does not follow the pattern of breakpoint sites and point mutations defined in other histologic subtypes of NHL with this translocation, suggest that the t(8;14) in these cases is cytogenetically and molecularly distinct from the t(8;14) seen in high-grade NHLs, and is relatively ineffectual in terms of MYC deregulation, or that other genetic elements at these chromosomal sites may be involved. Further analysis of these tumors may provide insights into MYC deregulation and BCL2-independent FL.

Aged↗

PubMed1992

Distinct patterns of chromosome abnormalities characterize childhood non-Hodgkin's lymphoma.

We report here cytogenetic studies of a series of 23 childhood non-Hodgkin's lymphomas (NHL), a group that has previously not been subjected to detailed cytogenetic analysis. Combining our results with data from 25 tumours in the published literature, we have performed the first cytogenetic analysis of a large series of childhood NHL. Our results show that the cytogenetic changes encountered in NHL of children are distinct and may be different from those seen in NHL of adults reflecting the previously recognized differences in histological presentation and clinical behaviour of the two entities. Thus, the most frequently occurring translocation in B-cell lesions in children was t(8;14)(q24;1q32). Other translocations frequently seen in adults such as t(14;18)(q32;q21),t(11;14)(q13;q32) and t(3;22)(q27;q11) were either rare or so far not seen in children, although reciprocal translocations appeared to be generally prevalent in childhood NHL. Combining our data with those in the published literature, we have identified two new recurring translocations [t(1;17)(p36;q21) and t(1;14)(p36;q22)], and a recurring duplication [dup(11)(q13;q23)] in this group of lymphomas. In addition, our literature survey identified a third recurring translocation [t(5;14)(q23;q32)] which was previously reported in two cases of childhood NHL. Our analysis also showed differences in the types of nonrandom translocations between childhood NHL and acute lymphoblastic leukaemia (ALL) in children suggesting that biologically these entities are different from one another. This study thus uncovers patterns of chromosome change associated with childhood lymphoma thus providing new opportunities for investigation of their clinical significance by correlation analysis and biological significance by molecular analysis.

Adolescent↗