Compendium of Cancer Genome Aberrations

HAEM5:Juvenile xanthogranuloma: Difference between revisions

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{{DISPLAYTITLE:Juvenile xanthogranuloma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
{{Under Construction}}
<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>
==Primary Author(s)*==
==Primary Author(s)*==


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|''CLTC::SYK'' fusions
|''CLTC::SYK'' fusions


Exon 5 or intron 5 of SYK that lead to fusion of ''CLTC'' exon 31 to ''SYK'' exon 6
Breakpoints in exon 5 or intron 5 of SYK (resulting in alternative splicing through exon skipping) lead to the fusion of SYK exon 6 to ''CLTC'' exon 31


ETV6::SYK fusion
ETV6::SYK fusion
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|Unknown
|Unknown
|A pediatric patient with systemic JXG, CNS lesions and  KIF5B-ALK fusion achieved clinical improvement with ALK-inhibitor Alectinib therapy. [7]
|A pediatric patient with systemic JXG, CNS lesions and  KIF5B-ALK fusion achieved clinical improvement with ALK-inhibitor Alectinib therapy. [7]
|A unique group of infants with an aggressive form of JXG with spleen, liver, and bone marrow showed infiltration with histiocytes with activating ALK fusions. [8] KIF5B–ALK seen in systemic JXG with CNS involvement. [7] child with JXG of soft tissue
|A unique group of infants with an aggressive form of JXG with spleen, liver, and bone marrow showed infiltration with histiocytes with activating ALK fusions. [8] KIF5B–ALK seen in systemic JXG with CNS involvement. [7]
|-
|-
|''MRC1::PDGFRB'' fusion
|''MRC1::PDGFRB'' fusion
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|Unknown
|Unknown
|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]
|Targeted therapy of treatment resistant systemic JXG with Dasatinib showed a steady and dramatic clinical response with a reduction in the size of the primary tumor. [9]
|A 3 month old female with a large JXG intra-abdominal tumor involving the greater omentum, intestinal walls and hepatic hilum achieved complete remission without relapse during 24 years of follow up. Testing showed a large deletion of exons 21 and 22 of CSF1R in parallel with MRC1::PDGFRB fusion. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] A child with chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib. [12]
|A 3 month old female with a large JXG intra-abdominal tumor involving the greater omentum, intestinal walls and hepatic hilum achieved complete remission without relapse during 24 years of follow up. Testing showed a large deletion of exons 21 and 22 of CSF1R in parallel with MRC1::PDGFRB fusion. [12] IHC staining showed diffuse expression of cyclin D1 in tumor cells.[9] A child with chemotherapy-refractory left chest wall JXG, MRC1::PDGFRB fusion was treated with dasatinib and demonstrated clinical and radiological reduction in size and metabolic activity of the tumor mass. [12]
|-
|-
|''TBL1XR1::BOD1L1'' fusion (and reciprocal BOD1L1::ABHD10)
|''TBL1XR1::BOD1L1'' fusion (and reciprocal BOD1L1::ABHD10)
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|Unknown
|Unknown
|May respond to targeted treatment with (MEK) inhibitors. [5]
|May respond to targeted treatment with (MEK) inhibitors. [5]
|Systemic juvenile xanthogranuloma [4]
|Systemic juvenile xanthogranuloma. [4]<br />
<br />
|-
|-
|''CSF1R'' mutations
|''CSF1R'' mutations
|Kinase driver mutations
|Kinase driver mutations
-Deletion in exon 12
Deletions in exon 12


-multiple missense mutations in exons 9 and 10
Multiple missense mutations in exons 9 and 10


-large deletion of exons 21 and 22  
Large deletions involving exons 21 and 22  


-Alternative CSF1R mutations in exons 9 and 10
Alternative CSF1R mutations in exons 9 and 10


-Missense mutations in exon 10
Missense mutations in exon 10 [12]
 
[12]
|Unknown
|Unknown
|Unknown
|Unknown
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|Unknown
|Unknown
|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]
|CSF-1R-specific small-molecule inhibitors Pexidartinib and BLZ945 is being studied. [11]
| -Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]
| Exon 10 mutations affect the extracellular region of CSF-1R and might enhance receptor dimerization. [12]
-Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation [12]
Large deletion of CSF1R exons 21 and 22 affects the intracellular c-CBL binding domain leading to defective receptor ubiquitination, and degradation. [12]
 


Children less than 2years of age with soft tissue involvement
Children less than 2 years of age with soft tissue involvement. [4] [12]
[4] [12]
|-
|-
|''PIK3CA'' mutations
|''PIK3CA'' mutations
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|Unknown
|Unknown
|Unknown
|Unknown
|
|Neurofibromatosis is associated with JXG.
|-
|-
|''KRAS''
|''KRAS''
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|Unknown.
|Unknown.
Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .
Targeted therapy with BRAF-inhibitor dabrafenib needs to be studied further .
|Pediatric cases with systemic JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. These cases needs to be  followed up, they probably represent Erdheim–Chester disease.[6]
|Cases of systemic pediatric JXG with CNS involvement and ''BRAF'' V600E mutations show male preponderance and are associated with aggressive disease at presentation. Erdheim–Chester disease is an important differential diagnosis. [6]
|}
|}
Note: A more extensive list of mutations can be found in Bioportal (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.
Note: A more extensive list of mutations can be found in Bioportal (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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==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


Other diagnostic tests like next-generation sequencing (NGS), whole exome sequencing, whole transcriptome sequencing and targeted DNA and/or RNA sequencing that can be helpful for identification of mutations in the ''RAS/RAF/MAPK/ERK'' and ''PI3K/AKT'' pathway genes or ''BRAF, ALK, RET'', and ''NTRK1'' gene rearrangements. These tests are currently not utilized for diagnosis given there are no recognized molecular diagnostic features.
Sequencing is not relevant to establishing the diagnosis, given there are no recognized molecular diagnostic features, but whole exome sequencing, whole transcriptome sequencing, and targeted DNA and/or RNA sequencing may identify ''BRAF, ALK, RET'', and ''NTRK1'' gene rearrangements or other variants that disrupt the ''RAS/RAF/MAPK/ERK'' and ''PI3K/AKT'' pathways.  


==Familial Forms==
==Familial Forms==
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