Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma).
(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)
Primary Author(s)*
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | B-cell lymphoid proliferations and lymphomas |
| Family | Mature B-cell neoplasms |
| Type | Marginal zone lymphoma |
| Subtype(s) | Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue |
WHO Essential and Desirable Genetic Diagnostic Criteria
(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)
| WHO Essential Criteria (Genetics)* | |
| WHO Desirable Criteria (Genetics)* | |
| Other Classification |
*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.
Related Terminology
(Instructions: The table will have the related terminology from the WHO autocompleted.)
| Acceptable | |
| Not Recommended |
Gene Rearrangements
Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE: ABL1 | EXAMPLE: BCR::ABL1 | EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. | EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: Common (CML) | EXAMPLE: D, P, T | EXAMPLE: Yes (WHO, NCCN) | EXAMPLE:
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference). |
| EXAMPLE: CIC | EXAMPLE: CIC::DUX4 | EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. | EXAMPLE: t(4;19)(q25;q13) | EXAMPLE: Common (CIC-rearranged sarcoma) | EXAMPLE: D | EXAMPLE:
DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references). | |
| EXAMPLE: ALK | EXAMPLE: ELM4::ALK
|
EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. | EXAMPLE: N/A | EXAMPLE: Rare (Lung adenocarcinoma) | EXAMPLE: T | EXAMPLE:
Both balanced and unbalanced forms are observed by FISH (add references). | |
| EXAMPLE: ABL1 | EXAMPLE: N/A | EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. | EXAMPLE: N/A | EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) | EXAMPLE: D, P, T | ||
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the previous version of the page. Please incorporate above.
| Chromosomal Rearrangement | Genes in Fusion
(5’ or 3’ Segments) |
Dysregulated pathway | Prevalence | Anatomic Sites | Notes |
|---|---|---|---|---|---|
| t(11;18)(q21;q21) | 5'BIRC3 (API2)-3'MALT1 | NF-κB | 15-40% | Stomach, lung, ocular adnexa | Associated with resistance to H. pylori eradication therapy |
| t(14;18)(q32;q21) | IGH-MALT1 | NF-κB | 10-15% | Ocular adnexa, skin, liver, salivary gland | Non-gastric MALT lymphoma
Associated with other karyotype abnormalities (trisomy) t(14;18)(q32;q21) IGH-MALT1 is indistinguishable from IgH / BCL2 by cytogenetics. |
| t(3;14)(p13;q32) | FOXP1-IGH | Wnt | ~5% | Thyroid, ocular adnexa, skin | not seen in gastric cases. Transcriptional deregulation of FOXP1 |
| t(1;14)(p22:q32) | BCL10-IGH | NF-κB | ~5% | Lung, small intestine | not seen in gastric cases. Transcriptional deregulation of BCL10 |
| t(X;14)(p11.2;q32) | GPR34-IGH | NF-κB? | ~2% | Lung, parotid gland | |
| t(1;2)(p22;q12) | BCL10-IGK | Unclear | ~1% | Stomach | |
| t(1;14)(p21;q32) | CNN3-IGH | NF-κB | Parotid gland | ||
| t(9;14)(p24;q32) | KDM4C-IGH | Chromatin remodeling[1] | Parotid gland, ocular adnexa | ||
| t(5;14)(q34;q32) | TENM2-IGH | Unclear | Skin, ocular adnexa | ||
| t(6;7)(q25;q11) | Unknown | Unclear | Ocular adnexa |
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editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.
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Individual Region Genomic Gain/Loss/LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE: No | EXAMPLE:
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add references). | |
| EXAMPLE:
17 |
EXAMPLE: Amp | EXAMPLE:
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb] |
EXAMPLE:
ERBB2 |
EXAMPLE: D, P, T | EXAMPLE:
Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined. | |
editv4:Individual Region Genomic Gain/Loss/LOHThe content below was from the previous version of the page. Please incorporate above.
| Chr # | Gain / Loss / Amp / LOH | Region | Possible Target Genes | Frequency | Notes |
|---|---|---|---|---|---|
| 3 | Gain | 3q | NFKBIZ, BCL6 | 30% | often associated with other translocations |
| 6 | Loss | 6q23 | TNFAIP3/A20 | 30% | often associated with other translocations |
| 3 | Gain | 3p | FOXP1 | 26% | often associated with other translocations |
| 6 | Gain | 6p25.1-p21.32 | unknown | unknown | |
| 18 | Gain | 18q | unknown | unknown | common secondary finding in B-cell neoplasm |
editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.
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Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | EXAMPLE: Common (Oligodendroglioma) | EXAMPLE: D, P | ||
| EXAMPLE:
Microsatellite instability - hypermutated |
EXAMPLE: Common (Endometrial carcinoma) | EXAMPLE: P, T | |||
Gene Mutations (SNV/INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| EXAMPLE:EGFR
|
EXAMPLE: Exon 18-21 activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (lung cancer) | EXAMPLE: T | EXAMPLE: Yes (NCCN) | EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references). |
| EXAMPLE: TP53; Variable LOF mutations
|
EXAMPLE: Variable LOF mutations | EXAMPLE: Tumor Supressor Gene | EXAMPLE: Common (breast cancer) | EXAMPLE: P | EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |
| EXAMPLE: BRAF; Activating mutations | EXAMPLE: Activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (melanoma) | EXAMPLE: T | ||
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editv4:Gene Mutations (SNV/INDEL)The content below was from the previous version of the page. Please incorporate above.
- MALT lymphoma presents somatically mutated immunoglobulin heavy chain variable region (IGHV) genes in nearly all cases. Site specific.[6]
- IGHVH1-69 in salivary gland lymphomas
- IGHVH3-30 or IGHVH3-23 in gastric MALT lymphomas responsive to H pylori eradication and without the t(11;18) translocation
- IGHVH4-34 in orbital adnexal lymphomas
- IGHV3 and IGHV4 families in pulmonary lymphomas
- IGHVH1-69 or IGHVH4-59 in cutaneous lymphomas
| Gene; Genetic Alteration | Presumed Mechanism
(Tumor Suppressor Gene [TSG] / Oncogene / Other) |
Prevalence | Notes |
|---|---|---|---|
| TNFAIP3 | NF-κB negative regulator | 29% | Mutations includes deletions, SNVs, and promoter methylation, can be present in cases lacking specific translocations listed above. Mutations can be also found in many types of NHL. |
| CREBBP | Tumor Suppressor | 22% | |
| KMT2C | Tumor Suppressor | 19% | |
| TET2 | Myelopoiesis | 17% | |
| SPEN | 17% | ||
| KMT2D | Histone modification | 15% | |
| LRP1B | 15% | ||
| PRDM1 | 15% | ||
| TNFRSF14 | NF-κB negative regulator | 11% | |
| NOTCH1/NOTCH2 | NOTCH signaling pathway | 11% | |
| PIM1 | |||
| cMyc | Oncogene | ||
| P53 | Tumor Suppressor | ||
| MYD88 | 6-9% | L265P |
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.
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Epigenomic Alterations
N/A
Genes and Main Pathways Involved
Put your text here and fill in the table
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
Put your text here (Instructions: Include recommended testing type(s) to identify the clinically significant genetic alterations.)
Familial Forms
No familial predisposition for MALT lymphomas has been reported.
Additional Information
N/A
Links
HAEM5:Nodal marginal zone lymphoma
HAEM5:Splenic marginal zone lymphoma
References
- ↑ Rui, Lixin; et al. (2010-12-14). "Cooperative epigenetic modulation by cancer amplicon genes". Cancer Cell. 18 (6): 590–605. doi:10.1016/j.ccr.2010.11.013. ISSN 1878-3686. PMC 3049192. PMID 21156283.
- ↑ Jump up to: 2.0 2.1 Troppan, Katharina; et al. (2015). "Molecular Pathogenesis of MALT Lymphoma". Gastroenterology Research and Practice. 2015: 102656. doi:10.1155/2015/102656. ISSN 1687-6121. PMC 4397421. PMID 25922601.
- ↑ Rinaldi, Andrea; et al. (2011-02-03). "Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome". Blood. 117 (5): 1595–1604. doi:10.1182/blood-2010-01-264275. ISSN 1528-0020. PMID 21115979.
- ↑ Zucca, Emanuele; et al. (2016-04-28). "The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance". Blood. 127 (17): 2082–2092. doi:10.1182/blood-2015-12-624304. ISSN 1528-0020. PMID 26989205.
- ↑ Jump up to: 5.0 5.1 Cascione, Luciano; et al. (2019-12). "Novel insights into the genetics and epigenetics of MALT lymphoma unveiled by next generation sequencing analyses". Haematologica. 104 (12): e558–e561. doi:10.3324/haematol.2018.214957. ISSN 1592-8721. PMC 6959164. PMID 31018978. Check date values in:
|date=(help) - ↑ Thieblemont, Catherine; et al. (2014-02). "Chronic inflammation and extra-nodal marginal-zone lymphomas of MALT-type". Seminars in Cancer Biology. 24: 33–42. doi:10.1016/j.semcancer.2013.11.005. ISSN 1096-3650. PMID 24333758. Check date values in:
|date=(help)
(use "Cite" icon at top of page)
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
*Citation of this Page: “Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 03/24/2025, https://ccga.io/index.php/HAEM5:Extranodal_marginal_zone_lymphoma_of_mucosa-associated_lymphoid_tissue.