Determination of clonality in patients who present with diagnostic dilemmas: a laboratory experience and review of the literature

Rockman, SP

doi:10.1038/sj.leu.2400678

Cited by 25 publications

(18 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the sensitivity of PCR in detecting clonal IgH rearrangement is strongly dependent on the relative number of polyclonal lymphoid cells, which are coamplified with the clonal population if present in the sample (24,33,34). As demonstrated in this study, these polyclonal lymphoid cells can be responsible for a pseudoclonal PCR profile (see Figs.…”

Section: Discussionmentioning

confidence: 60%

See 1 more Smart Citation

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

et al. 2000

View full text Add to dashboard Cite

This report summarizes a cumulative 4-year experience in polymerase chain reaction (PCR) analysis of immunoglobin heavy chain (IgH) and TcR-␥ chain gene rearrangements in 525 cases of lymphoproliferative disorders. Because the sensitivity of the PCR methodology was found to be tissue dependent, in the study of the presence of clonal cell population in tissues containing a small number of polyclonal lymphocytes, such as skin and gastrointestinal biopsy specimens, we used the multiple-PCR run approach. In this latter methodology, we repeat the PCR reaction from the same sample at least three times to confirm the reproducibility of the results. In the study of 273 cases of B-or T-cell lymphomas with characteristic immunomorphological and clinical features, a clonal IgH or TcR-␥ chain gene rearrangement was detected in approximately 80% of cases. A clonal rearrangement involving both IgH and TcR-␥ chain genes was found in 10% of cases of both B-cell and T-cell lymphomas. The study of 167 cases of nonneoplastic lymphoid tissue samples showed the presence of clonally rearranged cell populations for IgH or TcR-␥ genes in 3 and 9% of cases, respectively. We also applied PCR for the study of 85 cases of lymphoproliferations with no definite diagnosis (i.e., benign versus malignant) after immunomorphological analysis. In 65 cases (76%), the correlation of immunomorphological features with the presence (48 cases) or the absence (17 cases) of clonal lymphoid cell populations led to a definite diagnosis. In almost all these cases, the final diagnosis was found to be in agreement with the clinical course. In the 20 remaining cases (24%), no definite diagnosis could be made. We also assessed the value of PCR in detecting bcl-2/J H gene rearrangement as an additional clonal marker in the diagnosis of follicular lymphoma. Bcl-2/J H rearrangement and/or IgH gene rearrangement was found in approximately 85% (71/85) of follicular lymphoma cases studied.

show abstract

Section: Discussionmentioning

confidence: 60%

“…As reported elsewhere, the sensitivity of the IgH and TcR-␥ PCR for the detection of a clonally rearranged cell population is tissue dependent (24,33,34). Indeed, this sensitivity is dependent on the number of polyclonal cells present in the sample, which is coamplified with the clonal cell population if present.…”

Section: Sensitivity Of Pcrmentioning

confidence: 82%

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

et al. 2000

View full text Add to dashboard Cite

show abstract

“…However, the interpretation of PCR products depends on the type of gel 29 In this scenario, one-peak area analysis gives an analytical parameter to evaluate IgH gene rearrangements in gastric lymphoid infiltrates. Because this method is independent from the type of electrophoresis used, one-peak area analysis might be useful to unify different current methods of IgH gene rearrangement among several laboratories.…”

Section: Discussionmentioning

confidence: 99%

Analytical Detection of Immunoglobulin Heavy Chain Gene Rearrangements in Gastric Lymphoid Infiltrates by Peak Area Analysis of the Melting Curve in the LightCycler System

Retamales

Rodríguez

Guzmán

et al. 2007

The Journal of Molecular Diagnostics

View full text Add to dashboard Cite

Because it is difficult to differentiate gastric mucosaassociated lymphoid tissue (MALT) lymphoma from chronic gastritis in gastric lymphoid infiltrates, molecular detection of monoclonality through immunoglobulin heavy chain (IgH) gene rearrangements is commonly performed. However, heterogeneity in the performance and results obtained from IgH gene rearrangements has been reported. To improve the accuracy in the diagnosis of gastric lymphoid infiltrates, we developed an analytical approach based on one-peak area analysis of the melting curve in the LightCycler System. Using a training-testing approach, the likelihood ratio method was selected to find a discriminative function of 4.64 in the training set (10 gastric MALT lymphomas and 10 chronic gastritis cases). This discriminative function was validated in the testing set (five gastric MALT lymphomas, six abnormal lymphocytic infiltrates with subsequently demonstrated gastric MALT lymphomas, and six cases of chronic gastritis). All but one case of gastric MALT lymphoma, as well as abnormal lymphocytic infiltrates, clustered under 4.64, and all chronic gastritis cases clustered above 4.64. These results were validated by conventional electrophoreses confirming one or two sharp bands in cases of gastric MALT lymphomas and a smear of multiple bands in cases of chronic gastritis. Analytical detection of IgH gene rearrangement in gastric lymphoid infiltrates by one-peak area analysis correctly distinguishes gastric MALT lymphomas from chronic gastritis, even in cases with diagnosis of abnormal lym-

show abstract

“…Since it is known that false-positive amplification is not uncommon in PCR of rearranged immunoglobulin genes, [35][36][37][38][39] we first examined the reliability of the isolated clones by ISH using CDR3 oligonucleotide probes. Subsequently, we analyzed the cloned sequences, focusing on their somatic mutations and intraclonal heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Primary Malignant Lymphoma of the Brain: Mutation Pattern of Rearranged Immunoglobulin Heavy Chain Gene

Endo

Zhang

Saito

et al. 2002

Japanese Journal of Cancer Research

View full text Add to dashboard Cite

Using reverse transcription-polymerase chain reaction (RT-PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B-cell lymphoma, were examined for rearranged V H -D-J H sequences of the immunoglobulin heavy chain gene, focusing on somatic mutations and intraclonal heterogeneity. The reliability of the isolated PCR clones was confirmed by in situ hybridization (ISH) with complementarity-determining region (CDR) 3 oligonucleotide probes. Sequence analysis of the PCR clones revealed a high frequency of somatic mutation, ranging from 8.8 to 27.3% (mean 18.2%) in the V H gene segments in all the lymphomas. A significantly lower frequency of replacement (R) mutations than expected was also seen in their frameworks (FRs) in all cases. These findings suggested that the precursor cells were germinal center (GC)-related cells in these lymphomas. However, despite extensive cloning experiments, intraclonal heterogeneity was not detected in any case except for one in which it could not be ruled out. Thus, it seemed likely that all of our brain lymphomas were derived from GC-related cells and that at least most of them were from post-GC cells. Key words: Lymphoma -Brain lymphoma -B-cell lymphoma -Immunoglobulin gene -In situ hybridizationPrimary brain lymphoma usually occurs in the brain parenchyma of aged patients whose general organs show no lymphoproliferative focus.1, 2) Pathologically, most brain lymphomas belong to the category of diffuse large B-cell lymphoma.3-5) The incidence of this tumor is low, accounting for about 1-3% of all intracranial tumors.2) However, a high incidence has been noted in immunodeficient patients.2) In addition, an increased incidence in nonimmunodeficient patients has recently been reported in several countries.2) Although the clinical, pathological, and immunological characteristics of this tumor have been adequately described, [1][2][3][4][5][6][7][8] there still remain a number of unsolved problems, including the histogenesis of the neoplastic B lymphocytes.In B lymphocytes in general, immunoglobulin heavy and light chain genes are rearranged. 9,10) In the heavy chain gene, 1 each of heavy chain variable (V H ), diversity (D) and joining (J H ) gene segments are chosen and assembled, resulting in a considerable variety of rearranged V H -D-J H gene sequences among B cells. 9,10) In addition, further variability is introduced by random deletions and insertions of nucleotides at V H -D and D-J H junctions 11,12) as well as by somatic mutations in the entire V H -D-J H sequence. [13][14][15] While V H -D-J H gene rearrangements, which are associated with random nucleotide deletions and insertions at the V H -D and D-J H junctions, occur at an earlier stage of B-cell differentiation, somatic mutations in the entire V H -D-J H sequences occur at a later stage when B cells are in the germinal center (GC) microenvironment of the lymphatic tissues. [13][14][15] Using polymerase chain reaction (PCR), recent studies of B-cell lymphomas have analyzed the rearranged immunoglobul...

show abstract

Determination of clonality in patients who present with diagnostic dilemmas: a laboratory experience and review of the literature

Cited by 25 publications

References 15 publications

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

PCR Analysis of Immunoglobulin Heavy Chain (IgH) and TcR-γ Chain Gene Rearrangements in the Diagnosis of Lymphoproliferative Disorders: Results of a Study of 525 Cases

Analytical Detection of Immunoglobulin Heavy Chain Gene Rearrangements in Gastric Lymphoid Infiltrates by Peak Area Analysis of the Melting Curve in the LightCycler System

Primary Malignant Lymphoma of the Brain: Mutation Pattern of Rearranged Immunoglobulin Heavy Chain Gene

Contact Info

Product

Resources

About