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R Coupland

Publications and source records attributed to R Coupland.

25 records · Page 2Linked to original sources
PubMed1988

Molecular genetics and the diagnosis of lymphoma.

Gene rearrangement analysis has emerged as a precise laboratory aid in the diagnosis and classification of malignant lymphoma and leukemia. Both clonality and lineage can be identified in lymphoid neoplasms by the demonstration of rearrangements of antigen receptor genes of the immunoglobulin supergene family--immunoglobulin and T-cell receptor genes. Rearrangement analysis is not only useful in differential diagnosis and classification, but also serves as a sensitive unique clonal marker to detect early occult recurrence in patients after therapy. In a similar manner, chromosomal translocations associated with specific disease types can be detected with DNA probes in Southern blot analysis without the use of conventional cytogenetics. Using this approach, one may diagnose specific chromosomal translocations associated with histologic types of lymphoma and leukemia. When appropriately applied, DNA rearrangement analysis complements conventional histology, immunophenotyping, and cytogenetics.

Biomarkers, Tumor↗
PubMed1988

Diagnostic interpretation of T gamma gene rearrangement: effect of polyclonal T cells.

Rearrangement of the T gamma gene, which encodes one chain of the second T-cell receptor, is an early event in the development of T lymphocytes. In contrast to the T-cell receptor beta chain gene, the T gamma gene contains a very limited V region gene repertoire, accounting for only 8 to 10 rearranging V gamma genes. As a consequence of the limited number of V gamma genes, only seven or eight nongermline restriction fragments are displayed, even by highly polyclonal T cells. Here, we demonstrate that T gamma gene analysis produces a picture of pseudoclonality among polyclonal T lymphocytes accompanying B-cell lymphoma, T-cell lymphoma, and Hodgkin's disease. As little as 10% contamination by polyclonal T lymphocytes is sufficient to detect rearrangements in both clinical samples and in a controlled sensitivity assay. Conversely, polyclonal T cells were found to obscure T-cell clones when polyclonal T cells represented as little as 30% of total cells. We conclude that, due to the unusual genomic structure of the T gamma gene, rearrangement analysis of the T gamma gene carries a significant limitation as a marker of clonality and lineage.

B-Lymphocytes↗
PubMed1984

Partial deletion of the beta-globin gene: a common beta-thalassaemia allele in Asian Indians.

We have examined 11 families of Asian Indian origin, who are segregating beta-thalassaemia alleles, for coupled restriction enzyme site markers. A beta-thalassaemia deletion allele, which removes over 600 base pairs, is a common cause of thalassaemia in this population. This deletion can be conveniently detected in AvaII restriction enzyme digests. Consequently AvaII digests are particularly informative in this population because both the deletion and a coupled restriction site polymorphism may be simultaneously observed.

Alleles↗
PubMedDate not supplied

Rearranging antigen-receptor genes in enriched Reed-Sternberg cell fractions of Hodgkin's disease.

Molecular genetic analysis of rearranging antigen-receptor genes in non-Hodgkin's lymphomas has revealed the clonality and lineage in the majority of cases. In an analogous approach, we sought to apply gene rearrangement analysis to Hodgkin's disease to understand better the clonality and origin of this disorder. However, the putative neoplastic cell of Hodgkin's disease, the Reed-Sternberg cell and its variants, is extraordinarily rare in most cases of Hodgkin's disease. On the average, Reed-Sternberg cells and variants represent 0.1 per cent of total cell suspensions of nodular sclerosing Hodgkin's disease. As this frequency is below the minimum threshold of sensitivity of the Southern blot assay, we attempted to enrich for Reed-Sternberg cells before DNA extraction and analysis. Using either elutrition or Percoll density gradient centrifugation, we were able to enrich the percentage of Reed-Sternberg cells and variants to above 1 per cent in five cases of nodular sclerosing Hodgkin's disease. In three of these cases, immunoglobulin gene rearrangements were identified, but no T cell receptor gene rearrangements were seen. No rearrangements were detected in unseparated cells or in the Reed-Sternberg cell-depleted fractions. In addition, the L428 Hodgkin's disease cell line was found to have one rearranged and one deleted heavy-chain gene, a rearranged kappa gene, a rearranged lambda gene, and a single rearranged beta allele. No rearrangements of the T gamma gene were found in L428. Taken together, these findings indicate that clonal cell populations are present in Hodgkin's disease and suggest the possibility of a clonally expanded lymphoid cell in this disorder.

Genes, Immunoglobulin↗
PubMedDate not supplied

Rearrangement, hypermutation, and possible preferential use of a VH5 gene, VH32, in a Hodgkin's cell line.

Nonrandom use of immunoglobulin variable (V) gene segments is a feature of some B-cell neoplasms, possibly as a consequence of antigen selection. In Hodgkin's disease, the primary tissues, cell lines, and even single Reed-Sternberg cells can carry immunoglobulin gene rearrangements. Here, we examined the immunoglobulin heavy-chain genes of a well-characterized Hodgkin's-derived cell line, L428, and found a hypermutated VH32 gene involving a conventional V(N)D(N)J4-C gamma 4 rearrangement. VH32 is one of two rearranging members of the VH5 family that is also rearranged preferentially in some B-cell neoplasms and familial CLL. Unexpectedly, the closest known rearranged sequence match for the rearranged VH gene of L428 was found in the single Reed-Sternberg cells of lymphocyte-predominance Hodgkin's disease, and is a mutated VH251, the only other rearranging member of the VH5 family. Assuming random usage of the human VH pool, the chance of coincident VH5 family gene rearrangement in the two cases of Hodgkin's disease is only about 10(-3). Biased use of VH genes suggests a B-cell target that is either selected by antigen or vulnerable to transformation at an early antigen-independent, developmental stage. These findings raise the question whether similar processes operate in Hodgkin's disease.

Base Sequence↗