t(14;18)(q32;q21) IGH/BCL2
t(2;18)(p11;q21) IGK/BCL2
t(18;22)(q21;q11) IGL/BCL2

1998-05-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

B- cell NHL mainly; may (rarely) be found in ALL or in chronic lymphoproliferative diseases

Phenotype stem cell origin

B lymphocyte; the translocation occurs at the pre B cell stage

Epidemiology

found in 80 to 90 % of follicular lymphomas, 30% of diffuse large cell lymphomas (sometimes with prior follicular type), rarely in other lymphoproliferative disorders

Prognosis

small cleaved cell follicular lymphomas have a slow evolutivity and a median survival of 10 yrs or more; large cell lymphomas have a worse prognosis; the t(14;18) may have little or no prognostic significance, which would be in accordance with its oncogenic role (see below)

Cytogenetics

Atlas Image
BAC248E24 (BCL2, 18q21, green) cohybridized with PAC PAC 998D24 (14q32.3, red, centromeric to the breakpoint) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

Cytogenetics morphological

the t(14;18) is well recognized with G-banding, may be overlocked with R-banding; the t(2;18)( p11;q21) and the t(18;22(q21;q11) are rare variants

Additional anomalies

found in 90% of cases; complex karyotypes are frequent; by decreasing order, +7, del(6q), +12, + X, + 18, +5, +8, + der(18), + 21 are found in 25 to 10% of cases; +X and del(6q) more frequently in low grade, +7,+8, +der(18), and also the addition of a t(8;14)(q24;q32) more often in high grade NHL

Genes Involved and Proteins

Gene name
IGH (Immunoglobulin Heavy)
Location
14q32.33
Dna rna description
IGH is composed of IGHV genes, IGHD segments, IGHJ segments, and IGHC genes.
Protein description
IGH encodes the immunoglobulin heavy chains. They result from the DNA rearrangement (with deletion of the intermediary DNA) of IGHV, IGHD and IGHJ; an additional DNA rearrangement (switch) with constant genes IGHM --> IGHG, IGHA and IGHE can occur.
Gene name
BCL2 (B-cell leukemia/lymphoma 2)
Location
18q21.33
Dna rna description
3 exons; 2 alternative transcripts (a and b)
Protein description
member of the BCL2 family (with BAX, BCLX,...); contains dimerization domains (BH) and NH domains; BCL2a contains a hydrophobic tail for membrane anchorage; inhibits cell death process through heterodimerization

Result of the Chromosomal Anomaly

Description

5 BCL2 translocated on chromosome 14 near JH (junctions genes of IgH) and C in 3; the breakpoint in BCL2 is either in the 3 untranslated region of exon 3 (major breakpoint region (MBR) in 70% of cases) or more distal, in 3 of exon 3 (minor cluster region (MCR) in the remaining 30%); illegitimate recombinationno fusion protein, but promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL2

Oncogenesis

as BCL2 is an apoptosis inhibitor, cell death is delayed, and there is cell accumulation more than real transformation (clones of long living B-cells with t(14;18) may even be seen in the normal population, and with frequency increasing with age)

Highly cited references

Pubmed IDYearTitleCitations
232971262013Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma.115
249431072014Double hit lymphoma: the MD Anderson Cancer Center clinical experience.106
220025752012B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome.56
237757152013A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma.26
251030702015B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas.21
249429412014Pathology of follicular lymphoma.18
250900262014MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified.16
262767702015B-acute lymphoblastic leukemia/lymphoblastic lymphoma.14
237726392014Molecular characteristics of diffuse large B-cell lymphoma in human immunodeficiency virus-infected and -uninfected patients in the pre-highly active antiretroviral therapy and pre-rituximab era.14
299037642018Inferior survival in high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements is not associated with MYC/IG gene rearrangements.13
290455412018From hepatitis C virus infection to B-cell lymphoma.13
215933462011Fluorescence in situ hybridisation analysis of formalin-fixed paraffin-embedded tissue sections in the diagnostic work-up of non-Burkitt high grade B-cell non-Hodgkin's lymphoma: a single centre's experience.12
226861902012In non-follicular lymphoproliferative disorders, IGH/BCL2-fusion is not restricted to chronic lymphocytic leukaemia.11
269655832016Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations.10
318079222020Subsequent development of histiocytic sarcoma and follicular lymphoma: cytogenetics and next-generation sequencing analyses provide evidence for transdifferentiation of early common lymphoid precursor-a case report and review of literature.8
327203482020Chronic lymphocytic leukemia patients with IGH translocations are characterized by a distinct genetic landscape with prognostic implications.7
331047942020Combined EZH2 and Bcl-2 inhibitors as precision therapy for genetically defined DLBCL subtypes.7
305751082019IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes.7
224315432012Composite chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma are biclonal lymphomas: a report of two cases.7
217905302011BIOMED-2 PCR assays for IGK gene rearrangements are essential for B-cell clonality analysis in follicular lymphoma.7
288733562017Follicular lymphoma with hyaline-vascular Castleman-like features: analysis of 6 cases and review of the literature.6
257430232015CD5-positive follicular lymphoma: clinicopathologic correlations and outcome in 88 cases.6
226235142013Follicular lymphoma transformed to "double-hit" B lymphoblastic lymphoma presenting in the peritoneal fluid.6
303223852018KRAS mutation in secondary malignant histiocytosis arising from low grade follicular lymphoma.5
286244742017"Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in vitro".5
271341112016Two cases of histiocytic sarcoma with BCL2 translocations and occult or subsequent follicular lymphoma.5
239162902013Prognostic implications of histologic grade and intensity of Bcl-2 expression in follicular lymphomas undergoing rituximab-containing therapy.5
228046882012High-grade B cell lymphoma, unclassifiable, with blastoid features: an unusual morphological subgroup associated frequently with BCL2 and/or MYC gene rearrangements and a poor prognosis.5
311603602019Elucidating a false-negative MYC break-apart fluorescence in situ hybridization probe study by next-generation sequencing in a patient with high-grade B-cell lymphoma with IGH/MYC and IGH/BCL2 rearrangements.4
266586642016Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases.4
253150782015Clinicopathological characteristics of follicular lymphoma with peripheral blood involvement.4
229683952012Frequencies of BCL2 and BCL6 translocations in representative Chinese follicular lymphoma patients: morphologic, immunohistochemical, and FISH analyses.4
215602522011Cytopathology of "double-hit" non-Hodgkin lymphoma.4
290820512017Primary Cutaneous Follicle Centre Lymphoma with Hodgkin and Reed-Sternberg Like Cells: A Case Report and Review of the Literature.3
239851732013Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia.3
236317222013Follicular lymphoma in Taiwan: a low frequency of t(14;18), with grade 3A tumours more closely related to grade 3B than to low-grade tumours.3
235213572013Clinicopathological prognostic indicators in 107 patients with diffuse large B-cell lymphoma transformed from follicular lymphoma.3
236666992013Molecular detection of t(14;18)(q32;q21) in follicular lymphoma.3
218377082011Establishment of a novel MALT lymphoma cell line, ma-1, from a patient with t(14;18)(q32;q21)-positive Helicobacter pylori-independent gastric MALT lymphoma.3
348020442022A novel diagnostic approach for the classification of small B-cell lymphoid neoplasms based on the NanoString platform.2
321967142020Clinicopathologic characteristics of follicular lymphoma in hepatitis C virus-infected patients.2
320311792020The broad landscape of follicular lymphoma: Part I.2
302544812018Coexistence of primary colorectal follicular lymphoma and multiple myeloma: a case report.2
299631402018Gastric follicular lymphoma: A report of 3 cases and a review of the literature.2
292174262018Composite lymphoma of follicular B-cell and peripheral T-cell types with distinct zone distribution in a 75-year-old male patient: a case study.2
265172962017Immunophenotypic and cytogenetic findings of B-lymphoblastic leukemia/lymphoma associated with combined IGH/BCL2 and MYC rearrangement.2
267197662015Rare double-hit with two translocations involving IGH both, with BCL2 and BCL3, in a monoclonal B-cell lymphoma/leukemia.2
253811332015A rare case of IGH/MYC and IGH/BCL2 double hit primary plasma cell leukemia.2
242347312014Current perspectives in genetics of "double-hit" lymphoma with possible clinical implications.2
239534192013Oral follicular lymphomas. A short report of 8 cases with assessment of the IGH/BCL2 gene fusion with fluorescence in situ hybridization.2
237829092013Acute EBV infection masquerading as "In-situ Follicular Lymphoma": a pitfall in the differential diagnosis of this entity.2
219976892011Clinicopathologic and genetic characterization of follicular lymphomas presenting in the ovary reveals 2 distinct subgroups.2
346240892022Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.1
339642772021Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma.1
337727302021Newly diagnosed follicular lymphoma during pembrolizumab treatment for lung cancer.1
332522762021CD10-Negative Primary Breast Follicular Lymphoma: A Rare Case of Primary Breast Lymphoma With an Atypical Immunophenotype Mimicking Marginal Zone Lymphoma.1
337777662021Case Report: Multiple Chromosomal Translocations Including Novel CIITA-CREBBP Fusion and Mutations in a Follicular Lymphoma.1
351164842021"Double hit" B-lymphoblastic lymphoma with concurrent IGH/BCL2 and 8q24/MYC translocations: a case report.1
325063202020Diffuse follicular lymphoma variant with a typical diagnostic pattern and an unusually aggressive clinical presentation.1
324593972020Establishment and characterization of a novel 'double-hit' follicular lymphoma cell line, FL-SJC.1
316317212020Primary Low-Grade B-Cell Lymphoma of Skull With Translocation Between Immunoglobulin and Interferon Regulatory Factor 4 Genes.1
293438802017Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection of Gene Translocation.1
280387092017Signet-ring cell lymphoma: clinicopathologic, immunohistochemical, and fluorescence in situ hybridization studies of 7 cases.1
286799882017Follicular lymphoma with plasmacytic differentiation accompanied by monoclonal IgG gammopathy.1
283210922017Refractory double-hit lymphoma/leukemia in childhood mimicking B-precursor acute lymphoblastic leukemia at initial presentation.1
269912672016Isolated Follicles Enriched for Centroblasts and Lacking t(14;18)/BCL2 in Lymphoid Tissue: Diagnostic and Clinical Implications.1
259939732015Fine needle aspiration cytology of histiocytic sarcoma with dendritic cell differentiation: a case of transdifferentiation from low-grade follicular lymphoma.1
258079172015Multiplex sequencing for EZH2, CD79B, and MYD88 mutations using archival cytospin preparations from B-cell non-Hodgkin lymphoma aspirates previously tested for MYC rearrangement and IGH/BCL2 translocation.1
255628172015Leukocyte common antigen (CD45) negative follicular lymphoma, a rare immunophenotypic presentation.1
246944812014Histiocytic sarcoma of the bile duct.1
231792092013[Round robin test for detection of genomic aberrations in non-Hodgkin lymphoma by in situ hybridization].1
235687222013[Immunophenotyping and molecular genetic analysis of diffuse large B-cell lymphoma].1
226845522012A single fusion signal for t(14;18)(q32;q21) translocation is present in both the follicular lymphoma and local endothelial cells.1
222576632012Primary follicular lymphoma of the epididymis positive for t(14;18)(q32;q21)/IGH-BCL2 and negative for BCL2 protein expression: a case report.1
215602512011Cytomorphologic findings of B-cell lymphomas with concurrent IGH/BCL2 and MYC rearrangements (dual-translocation lymphomas).1
357200062022IGH Translocations in Chinese Patients With Chronic Lymphocytic Leukemia: Clinicopathologic Characteristics and Genetic Profile.0
352975662022Clinicopathological analysis of follicular lymphoma with BCL2, BCL6, and MYC rearrangements.0
350306322022Distinct clinical and genetic features of hepatitis B virus-associated follicular lymphoma in Chinese patients.0
345286802022Recurrent Chromosomal Abnormalities in Tissues Involved by Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.0
338295122021Bcl-2-negative IGH-BCL2 translocation-negative follicular lymphoma of the thyroid differs genetically and epigenetically from Bcl-2-positive IGH-BCL2 translocation-positive follicular lymphoma.0
336761712021From the archives of MD Anderson Cancer Center: A case of concurrent follicular lymphoma and Langerhans cell sarcoma with a review of the literature.0
337869072021Primary cutaneous follicle center lymphoma with extensive plasmacytic differentiation and t(14;18) in both the lymphoid and plasma cell components.0
329553822021Lymphoma-like double-hit genetic abnormalities (MYC/IGH and IGH/BCL2) in a case of non-secretory multiple myeloma.0
328603762020Frequent loss of CD10 expression in follicular lymphoma with leukaemic presentation.0
328434542020High-grade B-cell lymphoma with MYC and BCL6 rearrangements presenting as a cervical mass.0
322025352020The broad landscape of follicular lymphoma: Part II.0
327133462020Transformation of a low-grade follicular lymphoma into a composite lymphoma combining a high-grade B-cell lymphoma and a lymphoblastic neoplasm expressing Terminal deoxynucleotidyl Transferase: a case report.0
315428522020A case of AL amyloidosis associated with follicular lymphoma with plasmacytic differentiation.0
317894082020Molecular and clinical progress in follicular lymphoma lacking the t(14;18) translocation (Review).0
308593982019Follicular lymphoma suggested to transform into EBV-negative plasmablastic lymphoma.0
299796132019Molecular Fingerprinting of Anatomically and Temporally Distinct B-Cell Lymphoma Samples by Next-Generation Sequencing to Establish Clonal Relatedness.0
316950022019[Aggressive B-cell lymphoma with IGH/MYC, IGH/BCL2, and IGH/CCND1 translocations].0
297935192018High-grade B-cell lymphoma with MYC and BCL2 rearrangements arising in a composite lymphoma.0
319381302018A case study of t(14;22)(q32;q11) involving immunoglobulin heavy and light chain in follicular lymphoma.0
285151002017Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA-Based Looped Ligation Assay (LOLA).0
306953132016[Case Conference of Hematological Malignancies Based on the Morphology of Blood Cells: Chairmen's Introductory Remarks].0
270950412016Clinicopathological prognostic factors of 24 patients with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.0
248817442014Rheumatoid arthritis/methotrexate-associated primary cutaneous diffuse large B-cell lymphoma, leg type.0
229146132013Usefulness of HGAL and LMO2 immunohistochemistry in the identification of follicular lymphomas of the non-gastric gastrointestinal tract.0
214919652011Primary high-grade B-cell lymphoma of the breast with concurrent IGH-BCL2 and MYC-IGL translocations in an adolescent patient.0

Article Bibliography

Pubmed IDLast YearTitleAuthors

Summary

Fusion gene

IGK/BCL2 IGK (14q32.33) BCL2 (18q21.33) M t(2;18)(p11;q21)

Note

the 3 translocations are variants of each other, and they share the same clinical significance
Atlas Image
t(14;18)(q32;q21) IGH/BCL2 , t(2;18)(p11;q21), t(18;22)(q21;q11), BCL2 Top: 14;18)(q32;q21), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen (left), and H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services (centre); - Courtesy Adriana Zamecnikova (bottom tree); R- banding - Jean Loup Huret (top), and Courtesy Hossein Mossafa (bottom). FISH - Courtesy Hossein Mossafa (center); Hybridization with Vysis LSI IGH/BCL dual color probe (Abbott Molecular, US) showing fused yellow signals on der(14) and der(18) chromosomes - Courtesy Adriana Zamecnikova. Middle: t(2;18)(p11;q21), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegent. Bottom: t(18;22)(q21;q11), G- banding - Courtesy Jean-Luc Lai and Alain Vanderhaegen (left) ; and, H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services (centre). BCL2: BAC248E24 (BCL2, 18q21, green) cohybridized with PAC PAC 998D24 (14q32.3, red, centromeric to the breakpoint) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

Citation

Jean-Loup Huret

t(14;18)(q32;q21) IGH/BCL2
t(2;18)(p11;q21) IGK/BCL2
t(18;22)(q21;q11) IGL/BCL2

Atlas Genet Cytogenet Oncol Haematol. 1998-05-01

Online version: http://atlasgeneticsoncology.org/haematological/2006/cancer-prone-explorer/case-report-explorer/js/lib/zoomerang.js