HAEM5:KSHV/HHV8-associated multicentric Castleman disease: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

<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:Multicentric Castleman Disease]].

|Category

|Tumour like lesions with B-cell predominance

|N/A

|Subtype(s)

|KSHV/HHV8-associated multicentric Castleman disease

==Related Terminology==

|+

|Acceptable

|HHV8-positive multicentric Castleman disease

|Not Recommended

|Plasmablastic multicentric Castleman disease

==Gene Rearrangements==

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)

|<span class="blue-text">EXAMPLE:</span> Common (CML)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)

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

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

|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''

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

|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)

|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)

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

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

 

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

|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''

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

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

|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|

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|

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|}

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!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

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

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

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

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

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

|<span class="blue-text">EXAMPLE:</span> No

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

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).

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

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

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

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

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

|

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

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

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==Characteristic Chromosomal or Other Global Mutational Patterns==

!Molecular Pathogenesis

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

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

|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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!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

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

|<span class="blue-text">EXAMPLE:</span> Common (lung cancer)

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

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

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

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

|<span class="blue-text">EXAMPLE:</span> Common (breast cancer)

|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

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

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

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

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

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

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

|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation

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

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

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

|<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

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<nowiki>*</nowiki>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 [[Leadership|''<u>Associate Editor</u>'']] 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.

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases K]]