HAEM5:Sezary syndrome: Difference between revisions

<blockquote class='blockedit'>{{Box-round|title=Content 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:Sézary Syndrome]].

<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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 to a table, click within the table and select the > symbol that appears to be given options. 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 </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

==Definition / Description of Disease==

 

 

 

==Synonyms / Terminology==

 

 

==Epidemiology / Prevalence==

|'''Signs and Symptoms'''

|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)

 

 

 

<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)

|'''Laboratory Findings'''

|<span class="blue-text">EXAMPLE:</span> Cytopenias

 

==Immunophenotype==

 

The clonal T lymphocytes (Sézary cells) are CD3+, CD4+, CD45(CLA)+ and CD8-.  They lack CD7 and CD26.  Almost all cases express PD1 (CD279), CCR4, and CCR7.  

 

Peripheral blood flow cytometry shows a CD4+/CD7- (>30%) or CD4+/CD26- (>40%) T-cell population<ref name=":0" />.

!Finding!!Marker

|Positive (universal)||CD3, CD4, CD45 (CLA), PD1 (CD279), CCR4, CCR7

|Positive (subset)||

|Negative (universal)||CD8, CD7, CD26

|-

Put your text here and fill in the table

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

|Yes

|No

|Yes

|<span class="blue-text">EXAMPLE:</span>

 

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Balanced translocations have not been detected in SS<ref name=":0" />.

Gene fusion between CTLA4 and CD28 is highly expressed. Additional fusion events include TYK2-UPF1, COL25A1-NFKB2, FASN-SGMS1, SMS1-ZEB1, SPATA21-RASA2, PITRM1-HK1, and BCR-NDUFAF6<ref name=":2" />.  

<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}

==Individual Region Genomic Gain / Loss / LOH==

!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

 

chr7:1- 159,335,973 [hg38]

 

|Yes

|No

 

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 reference).

 

chr8:1-145,138,636 [hg38]

 

|No

|No

 

Common recurrent secondary finding for t(8;21) (add reference).

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Somatic duplications can be found ranging from duplications of chromosome bands (8p23.3-q24.3, 17p11.2-q23.2) to entire chromosomes (chr 18). Several somatic deletions have also been demonstrated including a 15-25 Mb deletion on 17p12-p13.3<ref name=":2" />.  

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|Yes

|No

|No

 

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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Numerical and structural alterations are common in SS.  These include loss of 1p, 6q, and 10q with gains of 7 and 8q<ref name=":4">{{Cite journal|displayauthors=1|last=Almeida|first=Ana|date=December 2015|title=The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome|url=|journal=Nature Genetics|volume=47|pages=|via=}}</ref><ref name=":0" />.  Isochromosome 17q is a recurrent finding in SS<ref name=":0" />.  

Deletions are often associated with loss of tumor suppressor genes such as recurrent deletions involving 17p13.1 (TP53), 13q14.2 (RB1), 10q23.3 (PTEN) and 12p13.1 (CDKN1B). Focal chromosome 2p23.3 deletions (DNMT3A) were observed.<ref name=":4" />  

==Gene Mutations (SNV / INDEL)==

!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

|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations

<span class="blue-text">EXAMPLE:</span>

 

EGFR; Exon 20 mutations

 

<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations

|<span class="blue-text">EXAMPLE:</span> TSG

|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

 

<span class="blue-text">EXAMPLE:</span> 30% (add Reference)

|<span class="blue-text">EXAMPLE:</span> IDH1 R123H

|<span class="blue-text">EXAMPLE:</span> EGFR amplification

|}

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.

 

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The mutational landscape of Sezary syndrome is complex and over 1000 different gene mutations have been identified. Mutational signature characterized by C>T substitutions at NpCpG trinucleotides and C>A substitutions at CpCpN trinucleotides and C>T substitutions at CpCpN and TpCpN trinulceotides have been identified<ref name=":4" />.

Mutations in epigenetic regulator genes including TET2, CREBPP, KMT2C (MLL3) histone H3 lysine 4 (H3K4) methyltransferase, WI/SNF, and NuRD chromatin-remodeling complexes have been demonstrated as well<ref name=":4" />.

Mutations in the p53, p15, p16, JunB, and PTEN genes are generally found in late-stage disease, suggesting that they are secondary genetic events after disease initiation<ref name=":3" />.

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>

|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations

|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}

Genes involved in NF-kB signaling, chromatin remodeling, and DNA damage response have also been found to be altered. Notably, alterations to signaling pathways including Jak/signal transducer and activator of transcription (STAT) signaling and cell-cycle checkpoint have been shown to be involved in the pathogenesis<ref name=":2" />.<br />

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases S]]