HAEM5:High grade B-cell lymphoma with 11q aberrations

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Burkitt-Like Lymphoma with 11q Aberration.

(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)*

Lauren Shealy, MD, Medical University of South Carolina

Daynna Wolff, PhD, Medical University of South Carolina

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	B-cell lymphoid proliferations and lymphomas
Family	Mature B-cell neoplasms
Type	Large B-cell lymphomas
Subtype(s)	High grade B-cell lymphoma with 11q aberrations

Related Terminology

Acceptable	Large B-cell lymphoma with 11q aberration
Not Recommended	Burkitt-like lymphoma with 11q aberration; MYC-negative Burkitt lymphoma (obsolete)

Gene Rearrangements

BLL-11q has no known gene fusions at this time.

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

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.

The table below represents the smallest reported minimal lost region and smallest reported minimal gain region. Other larger MGR and MLR have been reported.

Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
11	Loss	chr11: 128,177,670-134,931,948	11q24.4q25	Yes	unknown	unknown
11	Gain	chr11: 117,815,640-119,275,901	11q23.3	Yes	unknown	unknown
11	minimal duplication region, 11.95 Mbp	ch11: 109,285,414-121,236,822	11q22.3q24.1	Yes	unknown	unknown	Minimal duplication region contained PAFAH1B2, USP2, and CBL oncogenes.

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

• Research up until this point has revealed no conservative breakpoints.

Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
proximal 11q duplications range in size often >50 Mbp or <20 Mbp and most often involving the 11q22.2.-23.2 can be as proximal as 11q13.3 often with inversion	yes	unknown	unknown	The characteristic gains combined with the terminal deletions can occur in the context of myc-positive BL and other myc-negative HGBCLs. The absence of a MYC translocation/amplification in association with this chromosomal pattern is critical to the provisional diagnosis of BLL-11q and may have prognostic and therapeutic implications, which are further discussed below. At least one case has been identified with only proximal gains in the context of UPD.
terminal 11q deletions range in size most often 11q24.1-24.3 noted to be as proximal as 11q23.3q25	yes	unknown	unknown
5q21.3q32 gain and 6q12.1-q21 loss	unknown	unknown	unknown	Noted to be recurrently concomitantly present with the characteristic proximal duplications and deletions that define BLL, 11q.

Notably, no 1q21 abnormalities were found in myc-negative, 11q positive cases.

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.

• Studies suggest an overall unique mutational profile, with little to no overlap with commonly mutated genes in DLCBL and BL, respectively. Notably, recurrent mutations in BL such as ID3, TCF3, and CCND3 were not present.
• Mutations listed below where noted to be recurrent in BLL-11q cases. Bold genes have also been found recurrently mutated in DLCBL.
  • DDX3X
  • ETS1 coding mutations located a DNA-binding domain, combined with lower RNA expression in BLL-11q cases
  • 7/15 cases showed mutations in GNA13
  • FOXO1
  • 3/15 cases showed a Y641 mutational hotspot mutation of EZH2
  • TTN

Recurrently mutated genes in BLL-11q with known mechanisms that may contribute to pathogenesis.

Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
BTG2; variable potential LOF mutations three missense mutations, 1 splice site deletion mutation	tumor suppressor gene via inhibition of CCND1 via pRb	4/11 cases	none known	none known	unknown	unknown	unknown
NFRKB **located in region of terminal deletion 3/4 were stop-gain mutations	gene associated with INO80 complex	4/15 cases	none known	none known	unknown	unknown	unknown	NFRKB is within the terminal deletion region, so these mutations would result in a biallelic loss. See main pathway involvement below.

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.

Epigenomic Alterations

• KMT2A has been found to be duplicated and occasionally amplified in numerous cases of BLL-11q
  • functions to methylate histones
• Found to have mutations in EP300, HIST1H1D, HIST1H2BC, CREBBP, KMT2C, EZH2, ARID1A, KMT2D

Genes and Main Pathways Involved

• Given the notable variations in size of the duplicated and deleted regions of BLL-11q, pathogenesis appears to be complex and remains to be elucidated. Still, it is presumed to be a a product of dosage effects produced by the more varied proximal duplications and more consistent terminal deletions.
• Genes found recurrently in minimal duplication region: IL10RA; TMPRSS4; SCN4B; AMICA1; MPZL3; CD3E; CD3D; UBE4A; ATP5L; KMT2A; TTC36, TMEM25, IFT46; ARCN1
• Genes found recurrently in terminal deleted region: ETS1; FLT1; KCNJ5; C11orf45; TP53AIP1
  • ETS1 and FLT1 are candidate tumor supressor genes thought to be involved in the pathogenesis of DLBCL

GENES with PROPOSED/KNOWN CANCER ASSOCIATIONS

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
IL10RA; Duplication	insulin receptor substrate-2/PI 3-kinase/AKT pathway	increase survival of progenitor myeloid cells
KMT2A; Duplication	methylation of histones (turns off genes)	amplification noted to be associated with bulky BLL-11q tumors >20 cm, mainly located in the retroperitoneum
USP2; duplication (found 1x)	deubiquitinase known to target proteins such as MDM2 (udiquinates p53), MDM4, and CCND1	increased degradation of p53 (less tumor suppressor) and more CCND1-->increased movement from G1 to synthesis
NFRKB; deleted	encodes a nuclear factor involved with the INO80 complex	altered transcriptional regulation

Genetic Diagnostic Testing Methods

• Conventional cytogenetics (karyotyping) + FISH using MYC break-apart probe to rule out MYC translocation
• Chromosomal microarray analysis

Familial Forms

• None known

Additional Information

Put your text here

Links

HAEM5:Burkitt lymphoma

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 Associate Editor or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

Prior Author(s):

*Citation of this Page: “High grade B-cell lymphoma with 11q aberrations”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 07/3/2025, https://ccga.io/index.php/HAEM5:High_grade_B-cell_lymphoma_with_11q_aberrations.

Other Sections

Cancer Sub-Classification/Subtype

Burkitt-like lymphoma with 11q aberration

Definition/Description of Disease

Rare aggressive mature B-cell lymphoma

Synonyms/Terminology

myc-negative Burkitt-like lymphoma (mnBLL, 11q)

non-myc Burkitt-like lymphoma (nmBLL)

BLL, 11q

BLL-11qHAEM5:Burkitt lymphoma

Clinical Implications

• Look for 11q aberration if Myc negative lymphoma with morphology reminiscent of BL, DLBCL, or HGBCL
• Attend to associated chromosomal and mutational abnormalities of other aggressive B-cell lymphomas, ensuring their absence before diagnosis of BLL-11q, since BLL-11q may represent
• BLL-11q patients treated with R-CHOP (DLBCL treatment) have a higher risk of relapse than those treated with traditional BL treatment

Tentatively appears to portend a better prognosis with high likelihood of years of remission

• 100% 2 year event free survival in pediatric cohort