Difference between revisions of "HAEM5:Systemic mastocytosis"

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{{DISPLAYTITLE:Systemic mastocytosis}}
 
{{DISPLAYTITLE:Systemic mastocytosis}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
  
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Systemic Mastocytosis]].
+
<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:Systemic Mastocytosis]].
 
}}</blockquote>
 
}}</blockquote>
 +
 +
<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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__TOC__
 
__TOC__
  
==Cancer Category / Type==
+
==WHO Classification of Disease==
  
Mastocytosis
+
{| class="wikitable"
 
+
!Structure
==Cancer Sub-Classification / Subtype==
+
!Disease
 
+
|-
Mastocytosis
+
|Book
 
+
|Haematolymphoid Tumours (5th ed.)
Systemic Mastocytosis
+
|-
 
+
|Category
Systemic Mastocytosis with an Associated Hematological Neoplasm
+
|Myeloid proliferations and neoplasms
 +
|-
 +
|Family
 +
|Mastocytosis
 +
|-
 +
|Type
 +
|N/A
 +
|-
 +
|Subtype(s)
 +
|Systemic mastocytosis
 +
|}
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
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==Clinical Features==
 
==Clinical Features==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
  
EXAMPLE B-symptoms (weight loss, fever, night sweats)
+
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
  
EXAMPLE Fatigue
+
<span class="blue-text">EXAMPLE:</span> Fatigue
  
EXAMPLE Lymphadenopathy (uncommon)
+
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
+
|<span class="blue-text">EXAMPLE:</span> Cytopenias
  
EXAMPLE Lymphocytosis (low level)
+
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
|}
 
|}
  
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==Immunophenotype==
 
==Immunophenotype==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
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Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
 
|-
 
|-
|Positive (subset)||EXAMPLE CD2
+
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
 
|-
 
|-
|Negative (universal)||EXAMPLE CD3
+
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
 
|-
 
|-
|Negative (subset)||EXAMPLE CD4
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|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
 
|}
 
|}
  
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|<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)
EXAMPLE 30% (add reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
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).
 
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).
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==Individual Region Genomic Gain / Loss / LOH==
 
==Individual Region Genomic Gain / Loss / LOH==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
7
 
7
|EXAMPLE Loss
+
|<span class="blue-text">EXAMPLE:</span> Loss
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7
 
chr7
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|Yes
 
|Yes
 
|No
 
|No
|EXAMPLE
+
|<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 reference).
 
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).
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
8
 
8
|EXAMPLE Gain
+
|<span class="blue-text">EXAMPLE:</span> Gain
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8
 
chr8
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|No
 
|No
 
|No
 
|No
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
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==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
  
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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'')</span>
+
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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. Do not delete table.'')</span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|No
 
|No
 
|No
 
|No
|EXAMPLE:
+
|<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).
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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==Gene Mutations (SNV / INDEL)==
 
==Gene Mutations (SNV / INDEL)==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references 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.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
|EXAMPLE: TP53; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
  
EXAMPLE:
+
<span class="blue-text">EXAMPLE:</span>
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
EXAMPLE: BRAF; Activating mutations
+
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|EXAMPLE: TSG
+
|<span class="blue-text">EXAMPLE:</span> TSG
|EXAMPLE: 20% (COSMIC)
+
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
  
EXAMPLE: 30% (add Reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|EXAMPLE: IDH1 R123H
+
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|EXAMPLE: EGFR amplification
+
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
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|TI
 
|TI
 
|16V8
 
|16V8
|EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
+
|<span class="blue-text">EXAMPLE:</span> Tumor Suppressor||<span class="blue-text">EXAMPLE:</span> LOF||<span class="blue-text">EXAMPLE:</span> 20%
 
|}
 
|}
 
 
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!Type!!Gene/Region/Other
 
!Type!!Gene/Region/Other
 
|-
 
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
+
|Concomitant Mutations||<span class="blue-text">EXAMPLE:</span> IDH1 R123H
 
|-
 
|-
|Secondary Mutations||EXAMPLE Trisomy 7
+
|Secondary Mutations||<span class="blue-text">EXAMPLE:</span> Trisomy 7
 
|-
 
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
+
|Mutually Exclusive||<span class="blue-text">EXAMPLE:</span> EGFR Amplification
 
|}
 
|}
  
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==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
  
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
+
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>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
+
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|-
 
|-
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|EXAMPLE:  Histone modification, chromatin remodeling
+
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|EXAMPLE:  Abnormal gene expression program
+
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
 
|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
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==Links==
 
==Links==
  
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
+
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "<nowiki>http://www</nowiki>." portion.'')</span>
  
 
==References==
 
==References==

Latest revision as of 17:16, 6 September 2024

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:Systemic Mastocytosis.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. 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 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Abdullah Osme, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University

Shashi Shetty, Ph.D. FACMG, FCCMG, University Hospitals Cleveland Medical Center, Case Western Reserve University

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category Myeloid proliferations and neoplasms
Family Mastocytosis
Type N/A
Subtype(s) Systemic mastocytosis

Definition / Description of Disease

The 2017 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors defines five subtypes of Systemic mastocytosis[1]

  1. Indolent systemic mastocytosis (including the bone marrow mastocytosis subtype)
  2. Smouldering systemic mastocytosis
  3. Systemic mastocytosis with an associated haematological neoplasm
  4. Aggressive systemic mastocytosis
  5. Mast cell leukaemia

The term systemic mastocytosis with an associated haematological neoplasm (SM-AHN) refers to cases with systemic mastocytosis and associated hematological neoplasms combination at the same time. In addition to systemic mastocytosis, usually a myeloid disease of non-mast cell lineage is detected, such as a myelodysplastic syndrome, myeloproliferative neoplasm, myelodysplastic/myeloproliferative neoplasm or acute myeloid leukaemia[2] .

This page will focus specifically only on systemic mastocytosis with an associated hematological neoplasm.

Synonyms / Terminology

Systemic mastocytosis with an associated clonal hematological non-mast cell lineage disease (SH-AHNMD)

Epidemiology / Prevalence

SM-AHN represents 5-40% of cases of systemic mastocytosis[3]

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Signs and Symptoms EXAMPLE: Asymptomatic (incidental finding on complete blood counts)

EXAMPLE: B-symptoms (weight loss, fever, night sweats)

EXAMPLE: Fatigue

EXAMPLE: Lymphadenopathy (uncommon)

Laboratory Findings EXAMPLE: Cytopenias

EXAMPLE: Lymphocytosis (low level)


editv4:Clinical Features
The content below was from the old template. Please incorporate above.

The clinical symptoms, disease course and prognosis is determined by both to systemic mastocytosis and to the associated haematological disorder[4] [5],[6]

Sites of Involvement

Similar to systemic mastocytosis and associated neoplasms.

Morphologic Features

Similar to systemic mastocytosis and associated neoplasms.

Immunophenotype

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Finding Marker
Positive (universal) EXAMPLE: CD1
Positive (subset) EXAMPLE: CD2
Negative (universal) EXAMPLE: CD3
Negative (subset) EXAMPLE: CD4

Chromosomal Rearrangements (Gene Fusions)

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) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

Yes No Yes 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).


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)

In systemic mastocytosis cases, an associated haematological neoplasm can be diagnosed before, simultaneously, or after. Any defined myeloid or lymphoid malignancy can occur as an associated haematological neoplasm, but most commonly myeloid neoplasms predominate, with chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasm, and unclassifiable are seen {1694,1696,1697, 3735,3751,3793}.

The most commonly detected AHN is chronic myelomonocytic leukaemia. Lymphoid neoplasms are rare.

The activating KIT D816V mutation is seen in most cases of SM-AHN, and usually this mutation is detectable in the systemic mastocytosis compartment and in the AHN cells. Additional mutations in other genes (e.g. TET2, SRSF2, ASXL1, CBL, RUNX1 and the RAS family of oncogenes) may also be detected depending based on the type of AHN. And these mutations will impact on the prognosis.

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)

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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

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

EXAMPLE:

chr7

Yes Yes 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 reference).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

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

EXAMPLE:

chr8

No No No EXAMPLE:

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

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: 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. Do not delete table.)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

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

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 and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.)

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
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).


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.


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.

The KIT gene mutation is useful in the diagnosis of systemic mastocytosis (SM) or mixed lineage hematopoietic neoplasms with a mast cell component and to stratify prognosis of core-binding factor (CBF) acute myeloid leukemia (AML).

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
TI 16V8 EXAMPLE: Tumor Suppressor EXAMPLE: LOF EXAMPLE: 20%

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE: IDH1 R123H
Secondary Mutations EXAMPLE: Trisomy 7
Mutually Exclusive EXAMPLE: EGFR Amplification

Epigenomic Alterations

Methylation status is not determined for SM-AHN.

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete 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

Genetic Diagnostic Testing Methods

Put your text here

Familial Forms

Unknown

Additional Information

Put your text here

Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. 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.)

  1. Arber DA, et al., (2017). Mastocytosis, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p 66-69.
  2. P, Valent; et al. (2001). "Diagnostic criteria and classification of mastocytosis: a consensus proposal". PMID 11377686.
  3. Ibrahim, Feryal A.; et al. (2020). "A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review". The American Journal of Case Reports. 21: e923354–1–e923354-9. doi:10.12659/AJCR.923354. ISSN 1941-5923. PMC 7252834 Check |pmc= value (help). PMID 32398637 Check |pmid= value (help).
  4. Kh, Lim; et al. (2009). "Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors". PMID 19363219.
  5. Horny, H-P; et al. (2004). "Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge". Journal of Clinical Pathology. 57 (6): 604–608. doi:10.1136/jcp.2003.014860. ISSN 0021-9746. PMC 1770310. PMID 15166264.
  6. Valent, P.; et al. (2014). "Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal". Annals of Oncology. 25 (9): 1691–1700. doi:10.1093/annonc/mdu047. ISSN 0923-7534. PMC 4155468. PMID 24675021.

Notes

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