Paediatric-type follicular lymphoma

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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:Paediatric-Type Follicular 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)*

  • Kathleen M. Schieffer, PhD
  • Ruthann Pfau, PhD, FACMG

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Mature B-cell neoplasms
Type Follicular lymphoma
Subtype(s) Paediatric-type follicular lymphoma

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


Other fusion partners include KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1

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 old template. Please incorporate above.
  • Negative for BCL2, BCL6, IGF4, IG@, and MYC rearrangement[1][2][3][4]
End of V4 Section


editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).
Please incorporate this section into the relevant tables found in:
  • Chromosomal Rearrangements (Gene Fusions)
  • Individual Region Genomic Gain/Loss/LOH
  • Characteristic Chromosomal Patterns
  • Gene Mutations (SNV/INDEL)
  • No genomic findings currently assist in diagnosis.
  • No differences in overall survival between patients with and without genomic alterations[4]
  • Activating alterations within the MAPK pathway alterations are frequently reported in PTFL which demonstrate constitutive activation of MEK/ERK signaling. Currently, the utility of MEK inhibitors, such as trametinib, in PTFL is not established.[2]
End of V4 Section

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:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.
  • Copy number alterations are uncommon (~0.5% of the genome)[2]
  • Copy neutral loss of heterozygosity (cnLOH) of 1p36 is most frequently reported, commonly overlapping the TNFRSF14 gene and frequently in patients with concomitant TNFRSF14 non-synonymous variation[2][3][4][5]
Chromosome Number Gain/Loss/Amp/LOH Region Reference
1p36 cnLOH overlapping TNFRSF14 gene [2][3][4][5]
1p36 Loss overlapping TNFRSF14 gene [3][4][5]
End of V4 Section

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
editv4:Characteristic Chromosomal Aberrations / Patterns
The content below was from the old template. Please incorporate above.
  • No characteristic chromosomal aberrations or patterns are described
End of V4 Section

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 old template. Please incorporate above.
  • Although alterations in chromatin-modifying genes, such as KMT2D, CREBBP, EP300, EZH2, are frequently described in adult follicular lymphoma[6][7], these genes are not recurrently altered in PTFL
  • PTFL frequently presents with somatic activating alterations in the MAPK signaling pathway[2][5]
  • Although IRF8 alterations in the C-terminal domain are described in adult follicular lymphoma and diffuse large B-cell lymphoma, the hotspot alteration p.K88R is specific to PTFL[2][8][5]
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) Reference(s)
MAP2K1 Exon 2 (p.F53Y, p.Q56P, p.K77E, p.K57R)

Exon 3 (p.C121S)

Oncogene Gain-of-function; Driver 43-49% [2][8][5]
TNFRSF14 Exons 1-3 inactivating mutations Tumor suppressor Loss-of-function; Driver 33-54% [2][3][4][5]
IRF8 p.K88R Other Loss-of-function; Driver 15-50% [2][8][5]
MAPK1 p.N297D, p.D321G Oncogene Gain-of-function; Driver 10% [2]
GNA13 Identified throughout the gene Tumor suppressor Loss-of-function 9-11% [3][5]

Other Mutations

Type Gene/Region/Other Reference(s)
Concomitant Mutations TNFRSF14 missense mutation and cnLOH [2][3][4][5]
Mutually Exclusive Oncogenic driver mutations (MAP2K1, MAPK1, RRAS) [2][5]
End of V4 Section

Epigenomic Alterations

  • Not applicable

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete 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
editv4:Genes and Main Pathways Involved
The content below was from the old template. Please incorporate above.
  • MAP2K1 encodes mitogen-activated protein kinase kinase 1 (also known as MEK1) involved in the MAPK signaling pathway. Oncogenic MAP2K1 alterations are predicted to constitutively activate the MAPK signaling pathway through ERK1/2 phosphorylation.[9]
  • TNFRSF14 encodes the tumor necrosis factor (TNF) superfamily member herpesvirus entry mediator (HVEM) involved in activating both inflammatory and inhibitory T-cell responses. TNFRSF14 alterations disrupt the interaction of TNFRSF14 and the immunoglobulin superfamily proteins B and T lymphocyte attenuator (BTLA) receptor, thereby abrogating B-cell receptor activation.[10][11]
  • IRF8 encodes interferon regulatory factor 8 primarily expressed in immune cells. In B cells, IRF8, in tandem with IRF4, plays a critical role in pre-B cell development.[12]
  • GNA13 encodes G protein subunit alpha 13 involved in signal transduction. GNA13 is expressed in germinal center B cells and is involved in sphingosine-1-phosphate signaling and germinal center confinement.[13][14]
End of V4 Section

Genetic Diagnostic Testing Methods

  • Histopathology and immunophenotyping

Familial Forms

  • Not applicable

Additional Information

  • Not applicable

Links

  • Put your links here (use "Link" icon at top of page)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)

  1. C, Agostinelli; et al. (2019). "Novel markers in pediatric-type follicular lymphoma". doi:10.1007/s00428-019-02681-y. PMC 6881426. PMID 31686194.CS1 maint: PMC format (link)
  2. Jump up to: 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 A, Louissaint; et al. (2016). "Pediatric-type nodal follicular lymphoma: a biologically distinct lymphoma with frequent MAPK pathway mutations". doi:10.1182/blood-2015-12-682591. PMC 5000844. PMID 27325104.CS1 maint: PMC format (link)
  3. Jump up to: 3.0 3.1 3.2 3.3 3.4 3.5 3.6 J, Schmidt; et al. (2016). "Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene". doi:10.1182/blood-2016-03-703819. PMC 5000845. PMID 27257180.CS1 maint: PMC format (link)
  4. Jump up to: 4.0 4.1 4.2 4.3 4.4 4.5 4.6 I, Martin-Guerrero; et al. (2013). "Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas". doi:10.3324/haematol.2012.073916. PMC 3729904. PMID 23445872.CS1 maint: PMC format (link)
  5. Jump up to: 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 J, Schmidt; et al. (2017). "Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation". doi:10.1182/blood-2017-03-776278. PMC 5520474. PMID 28533310.CS1 maint: PMC format (link)
  6. J, Okosun; et al. (2014). "Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma". doi:10.1038/ng.2856. PMC 3907271. PMID 24362818.CS1 maint: PMC format (link)
  7. Mr, Green; et al. (2015). "Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation". doi:10.1073/pnas.1501199112. PMC 4364211. PMID 25713363.CS1 maint: PMC format (link)
  8. Jump up to: 8.0 8.1 8.2 Mg, Ozawa; et al. (2016). "A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma". doi:10.1038/modpathol.2016.102. PMC 5047957. PMID 27338637.CS1 maint: PMC format (link)
  9. Yaeger, Rona; et al. (2019). "Targeting Alterations in the RAF–MEK Pathway". Cancer Discovery. 9 (3): 329–341. doi:10.1158/2159-8290.CD-18-1321. ISSN 2159-8274. PMC 6397699. PMID 30770389.CS1 maint: PMC format (link)
  10. S, Ma; et al. (2008). "Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development". doi:10.1182/blood-2007-08-110106. PMC 2214771. PMID 17971486.CS1 maint: PMC format (link)
  11. S, Ma; et al. (2006). "IFN regulatory factor 4 and 8 promote Ig light chain kappa locus activation in pre-B cell development". PMID 17114461.
  12. Mw, Steinberg; et al. (2011). "The signaling networks of the herpesvirus entry mediator (TNFRSF14) in immune regulation". doi:10.1111/j.1600-065X.2011.01064.x. PMC 3381650. PMID 22017438.CS1 maint: PMC format (link)
  13. Ja, Green; et al. (2012). "S1PR2 links germinal center confinement and growth regulation". doi:10.1111/j.1600-065X.2012.01114.x. PMC 3335345. PMID 22500830.CS1 maint: PMC format (link)
  14. J, Shimono; et al. (2018). "Analysis of GNA13 Protein in Follicular Lymphoma and its Association With Poor Prognosis". doi:10.1097/PAS.0000000000000969. PMC 6266301. PMID 30307409.CS1 maint: PMC format (link)


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: “Paediatric-type follicular lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/11/2025, https://ccga.io/index.php/HAEM5:Paediatric-type_follicular_lymphoma.