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BIOMARKER:

IGH translocation

i
Other names: IGH, Immunoglobulin Heavy Locus, Immunoglobulin Heavy Polypeptide, Joining Region, Immunglobulin Heavy Chain Variable Region, Immunoglobulin Heavy Diversity Cluster, Immunoglobulin Heavy Variable Cluster, D (Diversity) Region Of Heavy Chains, Immunoglobulin Heavy Diversity Group, Immunoglobulin Heavy Diversity Locus, Immunoglobulin Heavy Joining Cluster, Immunoglobulin Heavy Variable Group, J (Joining) Region Of Heavy Chains, Immunoglobulin Heavy Joining Group, Immunglobulin Heavy Chain, IGH.1@,
Entrez ID:
3ms
Chromosomal defects in multiple myeloma. (PubMed, Blood Rev)
Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.
Review • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
MYC translocation • IGH translocation
5ms
Primary central nervous system marginal zone lymphoma. (PubMed, Br J Haematol)
Short follow-up is a major limitation in reported PCNSMZL cases, which restrains our knowledge on long-term results and iatrogenic sequels. This review was focussed on presentation, differential diagnoses, pathological findings, treatment options and clinical outcomes of PCNSMZL; recommendations for best clinical practice are provided.
Review • Journal
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CD20 (Membrane Spanning 4-Domains A1) • NOTCH2 (Notch 2) • TNFAIP3 (TNF Alpha Induced Protein 3) • MALT1 (MALT1 Paracaspase)
|
IGH translocation
5ms
Novel identification of t(14;18)(q32;q21)/IGH::MALT1 in chronic lymphocytic leukaemia. (PubMed, Br J Haematol)
Both cases in this report were associated with lower-risk biological parameters. Thus, FISH testing for MALT1 in cases with unknown IGH translocation partners in the setting of CLL should be implemented in clinical practice to better define such cases.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • IGH (Immunoglobulin Heavy Locus) • MALT1 (MALT1 Paracaspase) • BCL3 (BCL3 Transcription Coactivator)
|
IGH translocation
5ms
MM-UMA PANEL, AN NGS APPROACH TO DEFINE THE MOLECULAR PROFILE OF MM PATIENTS: INTRA AND INTER LABORATORY VALIDATIONS’ RESULTS (SIE 2023)
A novel NGS targeted panel was designed and successfully validated, whose main novelty resides in the possibility to call CNAs from off-target reads, that can be used to define MM pts’ genomic risk factors, possibly required in the daily clinical practice. Thanks to AIRC IG2018-22059, AILBolognaODV.
Clinical • Next-generation sequencing
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)
|
TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • IGH translocation
6ms
Single Cell Whole Genome Measurement of Genomic Heterogeneity and Clonal Evolution in Multiple Myeloma (ASH 2023)
We applied DLP to 7 MM patients obtaining 800-1600 single cell whole genomes per patient. All canonical IgH translocations identified by FISH were recovered in the scWGS data. Single cell copy number heterogeneity was observed in all but 1 patient, including heterogeneity affecting known drivers.
IO biomarker
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TNFRSF17 (TNF Receptor Superfamily Member 17) • SDC1 (Syndecan 1)
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APOBEC mutagenesis • IGH translocation
6ms
The Complex Structural Variant Chromothripsis Can be Defined on Targeted Sequencing Panels, Allowing Direct Clinical Translation in Order to Improve Multiple Myeloma Prognostication (ASH 2023)
From 420 samples, 48 were collected at the precursor stage, 205 with NDMM, and 167 with relapsed disease. 39 patients had 2 assays performed, while the remainder were unique patient samples. Within NDMM, the range of induction regimens received included lenalidomide and dexamethasone with bortezomib (VRd), carfilzomib (KRd) or daratumumab (DRd), along with quadruplet therapy (DVRd or DKRd).
Clinical
|
TP53 (Tumor protein P53)
|
IGH translocation
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lenalidomide • bortezomib • Darzalex (daratumumab) • carfilzomib • dexamethasone
7ms
Internal Tandem Duplications of the BCMA Transmembrane Domain are Common in Hyperdiploid Multiple Myeloma and Associated with Constitutive NF-kB Signaling (IMW 2023)
As we begin to prioritize the use of different immune-based therapies it will be important to consider the relative risk each patient has to develop resistance based on the preexisting loss of one target gene copy, as some targets are frequently lost (GPRC5D) while others are rarely lost (FCRL5). Some hyperdiploid patients have hyperactivation of NF-kB signaling as a result of BCMA overexpression by high level copy number gains and immunoglobulin translocations or ITD. These patients are likely dependent on BCMA mediated signaling and would likely be exquisitely sensitive to BCMA targeted therapies.
IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • TNFRSF17 (TNF Receptor Superfamily Member 17)
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IGH translocation
7ms
High-risk cytogenetic abnormalities in Multiple Myeloma: PETHEMA-GEM experience. (IMW 2023)
In conclusion, our study confirmed the prognostic significance of high-risk cytogenetic abnormalities in a large cohort of MM patients. We also demonstrated the importance of considering the co-occurrence of high-risk alterations to accurately assess prognosis. Thus, while del(17p) retains its adverse prognosis even as a solitary abnormality, the negative prognosis of 1q gains was mitigated if this abnormality occured as the sole aberration.
IO biomarker
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CD38 (CD38 Molecule)
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IGH translocation • Chr del(1p)
7ms
Demographic and Clinical Characteristics of Multiple Myeloma Patients in a Tertiary Cancer institute of India (IMW 2023)
Our study highlights earlier age of presentation, higher incidence of end organ damage due to myeloma. A low incidence of high risk cytogenetic abnormalities was detected which resulted in a maximum number of patients in R-ISS II category. Though limited by retrospective nature and patient population from a tertiary care institute, the study suggests the need for prospective registry studies to document the potential difference in presentation among Indian patients and need for awareness about myeloma for early diagnosis.
Clinical
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TP53 (Tumor protein P53)
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IGH translocation
8ms
The prognostic impact of t(11;14) in multiple myeloma: A real-world analysis from the Australian Lymphoma Leukaemia Group (ALLG) and the Australian Myeloma and Related Diseases Registry (MRDR). (PubMed, EJHaem)
Eleven patients had received venetoclax with 45% achieving better than a very good partial response. Results suggest that t(11;14) MM may confer an unfavorable risk profile and that the use of targeted therapies such as venetoclax earlier in the treatment algorithm should be explored.
Journal • Real-world evidence • Real-world
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Chr t(11;14) • IGH translocation
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Venclexta (venetoclax)
11ms
Mitotic recombinatory evolution in acute leukemia. (PubMed, Cancer Genet)
Although selection-based HMR can effectively initiate at any site proximal to a driver gene fusion, it appears that the translocation breaksite is common for many translocations. In addition, evidence from HMR evolution related distal 11q mutations, numerous unbalanced CCND1/IGH translocations, and the double MAML2/KMT2A presented in this study suggest that a recombinatorial "hot spot" exists near the CCND1 gene in many rearrangements or mutations within 11q.
Journal
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CCND1 (Cyclin D1) • KMT2A (Lysine Methyltransferase 2A) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • AFDN (Afadin, Adherens Junction Formation Factor) • MAML2 (Mastermind Like Transcriptional Coactivator 2)
|
IGH translocation
11ms
Conditional survival in multiple myeloma and impact of prognostic factors over time. (PubMed, Blood Cancer J)
Among MM patients, 5-year CS was stable at 1-5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.
Journal
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IGH translocation
11ms
CLINICAL IMPLICATION OF CYTOGENETIC ABERRATIONS IN NON-AL AMYLOIDOSIS MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A MULTI- CENTER CHINESE CASE SERIES (EHA 2023)
61.3% non-AL-type amyloidosis-MGRS patients had IgH recombination, with t (11; 14) (q13; q32) the most common. Patients with t (11; 14) may have inferior renal responses to bortezomib-based treatment. Multiple myeloma
Clinical
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SDC1 (Syndecan 1)
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IGH translocation
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bortezomib
12ms
Improvement of diagnosis in children with Burkitt lymphoma in Kenya: feasibility study for the implementation of fluorescence in situ hybridisation testing for MYC and the MYC/IGH translocation. (PubMed, Ecancermedicalscience)
FISH testing was established, and a pilot study performed, to assess the feasibility of FISH as a diagnostic tool for the determination of BL in a Kenyan paediatric population. This study supports FISH in limited resource settings to improve the accuracy and speed of diagnosis of BL in Africa.
Journal
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CD20 (Membrane Spanning 4-Domains A1) • MME (Membrane Metalloendopeptidase)
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CD20 positive • IGH translocation
1year
Genomic and proteomic characterization of Philadelphia-like B-lineage acute lymphoblastic leukemia: A report of Indian patients. (PubMed, Cancer)
In developing countries, detecting Philadelphia (Ph)-like B-lineage acute lymphoblastic leukemia is complicated and challenging due to its diverse genetic landscape. There is no well-defined and cost-effective methodology for its detection. The incidence of this high-risk subtype is very high in adult cases, and there is an urgent need for its accurate detection. We have developed an online PHi-RACE classifier for its rapid detection, followed by delineating the genomic and proteomic landscape of Ph-like acute lymphoblastic leukemias for the first time in Indian patients.
Journal
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JAK2 (Janus kinase 2) • CRLF2 (Cytokine Receptor Like Factor 2) • P2RY8 (P2Y Receptor Family Member 8) • IGKC (Immunoglobulin Kappa Constant) • NDUFA2 (NADH:Ubiquinone Oxidoreductase Subunit A2)
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CRLF2 overexpression • IGH translocation • JAK2 rearrangement
1year
Imaging flow cytometry-based multiplex FISH for three IGH translocations in multiple myeloma. (PubMed, J Hum Genet)
Moreover, the ISM-FISH showed a positive concordance of 96.6% and negative concordance of 98.8% with standard DC-FISH examining 1000 interphase cells. In conclusion, the ISM-FISH is a rapid and reliable diagnostic tool for the simultaneous examination of three critically important IGH translocations, which may promote risk-adapted individualized therapy in MM.
Journal
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FGFR3 (Fibroblast growth factor receptor 3) • CCND1 (Cyclin D1) • SDC1 (Syndecan 1)
|
Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • Chr t(11;14)(q13;q32) • IGH translocation • SDC1 positive
1year
Cytogenetic Abnormalities in Multiple Myeloma: Incidence, prognostic significance and geographic heterogeneity in Indian and western population. (PubMed, Cytogenet Genome Res)
In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% cases , of which 44% revealed highly complex karyotype with common aberrations of chromosome 1q. Overall FISH was found to be novel , easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease which in future in combination with mutation profile and Gene expression profile will help in further refinement of disease & identification of actionable targets.
Journal
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TP53 (Tumor protein P53)
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Chr del(17p) • Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • IGH translocation • Chr t(14;20)
over1year
Genome-Wide Methylation and Haplotype-Resolved Aberrant Somatic Hypermutation Patterns in B-Cell Lymphomas (ASH 2022)
The association of hypomethylated superenhancers, promoters, and CpG islands with genes over-expressed in DHITsig+ suggests these methylation patterns may contribute to the DHITsig phenotype. These results may aid in improving GCB DLBCL patient classification and reveal factors contributing to its heterogeneity.
IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • TCF3 (Transcription Factor 3) • IL1R1 (Interleukin 1 receptor, type I)
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IGH translocation • BCL2 translocation
over1year
A Single Next Generation Sequencing Assay for Detection of Driver Mutations, Translocations and Copy Number Alterations in Patients with Multiple Myeloma (ASH 2022)
Therefore, in addition to the detection of clinically relevant somatic mutations, the targeted NGS approach showed robust detection of recurrent MM specific IgH translocations and CNV. Furthermore, the detection of relevant abnormalities not routinely assessed in most clinical labs, such as TP53 bi-allelic inactivation, IgL and MYC rearrangements, supports the use of this small, targeted panel as a clinically relevant, single molecular assay, for the comprehensive profiling of MM.
Clinical • Next-generation sequencing
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • IGH (Immunoglobulin Heavy Locus) • SDC1 (Syndecan 1) • TENT5C (Terminal Nucleotidyltransferase 5C)
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TP53 mutation • KRAS mutation • Chr del(17p) • MYC rearrangement • NRAS G13 • MYC translocation • IGH translocation
over1year
Tracking the Earliest Genomic Events in Multiple Myeloma Life-History (ASH 2022)
Due to the development of a new WGS-based chronological model, we revealed the existence of SV acquired before canonical "MM-initiating" events in newly diagnosed MM patients. This data suggests that there may be alternative, previously undescribed, MM-initiating events, which can be explored in a lager dataset using our novel analytical methods.
IO biomarker
|
ATM (ATM serine/threonine kinase) • CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • CD38 (CD38 Molecule) • BIRC3 (Baculoviral IAP repeat containing 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SDC1 (Syndecan 1) • TCF3 (Transcription Factor 3)
|
IGH translocation
over1year
TP53 Gene Deletion or Mutation in Newly Diagnosed Multiple Myeloma Patients By FISH with Cytoscan Arrays and Targeted Panel Sequencing (ASH 2022)
This study comprehensively describes the detection of genetic abnormalities and prognostic survival analysis of NDMM patients by using FISH, CytoScan and targeted panel sequencing. Identifying the real high-risk patients, we can earlier take targeted and more active measures, such as intensive induction treatment, tandem transplantation or CART treatment, to better deepen and consolidate the therapeutic effect for long-term survival benefits of patients.
Clinical
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TP53 (Tumor protein P53) • SDC1 (Syndecan 1)
|
TP53 mutation • TP53 deletion • IGH translocation
over1year
Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies. (PubMed, Cancer Sci)
The proportion of patients with clinically relevant alterations was the highest in acute myeloid leukemia, while this assay was less informative in T/NK-cell lymphoma. These results suggest the clinical utility of NGS-based genomic profiling, particularly for their diagnosis and prognostic prediction, thereby highlighting the promise of precision medicine in hematological malignancies.
Journal
|
IGH (Immunoglobulin Heavy Locus) • IKZF1 (IKAROS Family Zinc Finger 1)
|
IGH translocation
over1year
Recurrent Novel P2RY8/IGH Translocations in B-Lymphoblastic Leukemia/Lymphoma. (PubMed, Front Oncol)
However, a high expression level of truncated P2RY8 was observed in the patients compared with healthy donors, which might be related to the aggressive clinical course and inferior outcome. In summary, we described recurrent novel P2RY8/IGH translocations with high expression levels of P2RY8, which may contribute to the guidelines for clinical diagnosis and treatment.
Journal
|
IGH (Immunoglobulin Heavy Locus) • CRLF2 (Cytokine Receptor Like Factor 2) • P2RY8 (P2Y Receptor Family Member 8)
|
IGH translocation
over1year
Daratumumab-bortezomib-dexamethasone (Dara-VCd) vs Bortezomib-Thalidomide-Dexamethasone (VTd), Then Maintenance With Ixazomib (IXA) or IXA-Dara (clinicaltrials.gov)
P2, N=401, Active, not recruiting, European Myeloma Network | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2022 --> May 2024
Enrollment closed • Trial primary completion date • Combination therapy
|
IGH (Immunoglobulin Heavy Locus)
|
IGH translocation
|
bortezomib • cyclophosphamide • Ninlaro (ixazomib) • Darzalex (daratumumab) • thalidomide • melphalan
almost2years
DOUBLE-HIT TRAF3 DELETION AND MUTATION IDENTIFIED BY HIGH-THROUGHPUT SEQUENCING DEFINE A NEW INDEPENDENT PROGNOSTIC FACTOR IN CHRONIC LYMPHOCYTIC LEUKEMIA (EHA 2022)
Conclusion Our work demonstrates that TRAF3 mutations and deletions are highly enriched in CLL patients with del-3’IGH, resulting in the biallelic inactivation of this gene. The presence of this double-hit on TRAF3 worsen the prognosis of CLL patients, being and independent prognostic factor with similar impact on TFT than the biallelic loss of TP53 .
TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • CD19 (CD19 Molecule) • IGH (Immunoglobulin Heavy Locus)
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ATM mutation • Chr del(11q) • IGH translocation
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Vysis CLL FISH Probe Kit
2years
CD37 expression in follicular lymphoma. (PubMed, Ann Hematol)
Therefore, CD37 protein may play a role in tumor progression and may serve as a therapeutic target. However, further studies are needed to explore its significance.
Retrospective data • Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
IGH translocation • BCL2 translocation
2years
Burkitt lymphoma: interpreting FISH testing for MYC gene rearrangements. (PubMed, BMJ Case Rep)
Additional testing with dual FISH probe detected MYC/IGH translocation. FISH testing using BAPs alone may be falsely negative for MYC translocations creating a diagnostic challenge and compromising the treatment approach and assessment of prognosis.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
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MYC rearrangement • MYC translocation • IGH translocation
over2years
t(9;14)(p13;q32)/PAX5-IGH translocation as a secondary cytogenetic abnormality in diffuse large B-cell lymphoma. (PubMed, J Clin Exp Hematop)
The breakpoints of t(9;14)(p13;q32) were mapped 2,170 bp upstream of the coding region of PAX5 alternative exon 1B and within the IGHJ6-Eμ enhancer intron of IGH. It is suggested that t(9;14)(p13;q32) in this case was a secondary cytogenetic abnormality and the translocation is not necessarily involved in initial malignant transformation of B-cells but can occur later during the course of diffuse large B-cell lymphoma.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6) • PAX5 (Paired Box 5) • CD5 (CD5 Molecule) • MME (Membrane Metalloendopeptidase)
|
CD20 positive • IGH translocation • BCL6 positive
over2years
The molecular ontogeny of follicular lymphoma: gene mutations succeeding the BCL2 translocation define common precursor cells. (PubMed, Br J Haematol)
Instead, we find cells harbouring the same BCL2/IGH translocation but lacking CREB binding protein (CREBBP), lysine methyltransferase 2D (KMT2D) and other recurrent gene mutations. Thus, (i) the BCL2/IGH translocation can precede CPC-defining mutations in human FL, and (ii) BCL2/IGH-translocated cells can persist in clinical remission.
Journal • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • IGH (Immunoglobulin Heavy Locus) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)
|
KMT2D mutation • IGH translocation • BCL2 translocation
over2years
Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma. (PubMed, Turk J Haematol)
Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of bone marrow biopsy and cytogenetic features of MM patients in our country.
Clinical • Journal • IO biomarker
|
IGH (Immunoglobulin Heavy Locus) • CD38 (CD38 Molecule)
|
IGH mutation • IGH translocation
over2years
[VIRTUAL] Impact of Cytogenetic Aberrations on Clinical Characteristics and Treatment Response in Indian Multiple Myeloma Patients: A Single Tertiary Center Experience (AMP 2021)
This study aimed to evaluate the association between cytogenetic abnormalities and clinicohaematological characteristics at diagnosis, and retrospectively compare the overall response rate to 2 triple drug combinations comprised of bortezomib, cyclophosphamide, and dexamethasone (VCd) versus thalidomide, cyclophosphamide, and dexamethasone (VRd) in transplant eligible patients with untreated MM. The key differences in baseline characteristics at presentation compared to Western population could be attributed to ethnic diversity. Triplet induction therapy VRd was superior as regards to response rates compared to VCd arm.
Clinical
|
TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • CCND1 (Cyclin D1) • B2M (Beta-2-microglobulin)
|
Chr t(11;14) • TP53 deletion • Chr t(4;14) • Chr t(14;16) • Chr t(11;14)(q13;q32) • IGH translocation • Chr t(14;20)
|
bortezomib • thalidomide
over2years
Purine Nucleoside Analogs Plus Rituximab Is an Effective Treatment Choice for Hairy Cell Leukemia-Variant: Results from a Single Center in China (ASH 2021)
Treatment choices included interferon-α (IFN-α) in 11 patients, chlorambucil (CLB) in 5 patients, single purine nucleoside analogs (PNA) in 3 patients and PNA plus rituximab in 9 patients. HCL-v is a rare disease with specific clinical and immunophenotypic features but may overlap with classic hairy cell leukemia or other splenic B-cell neoplasms. Overall, it is an indolent lymphoma with recurrent progression, and the use of PNA plus rituximab in first-line treatment can result in a deeper and longer remission.
Clinical
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • IGH (Immunoglobulin Heavy Locus) • CD79B (CD79b Molecule) • CD22 (CD22 Molecule) • IL2RA (Interleukin 2 receptor, alpha) • CD200 (CD200 Molecule) • ANXA1 (Annexin A1) • ITGAE (Integrin Subunit Alpha E) • IFNA1 (Interferon Alpha 1) • FCER2 (Fc Fragment Of IgE Receptor II)
|
TP53 mutation • BRAF V600E • TP53 deletion • IGH translocation
|
Rituxan (rituximab) • Leukeran (chlorambucil)