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<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>

<span style="color:#0070C0">(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 [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], 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 </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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==Chromosomal Rearrangements (Gene Fusions)==

==WHO Essential and Desirable Genetic Diagnostic Criteria==

<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>

 

==Gene Rearrangements==

Acute myeloid leukaemia (AML) with NUP98 rearrangement is characterized by chromosomal translocations involving NUP98 (nucleoporin 98 kDa) on chromosome 11p15.4 and various partner genes. (Reference WHO book). There are over 40 fusion partners which have been reported to date. NUP98 fusions can be categorized into three broad parts. The first category includes NUP98 fusions with transcription factors as partners, which can change the expression of target genes through DNA binding domains. The second category is NUP98 fusions with epigenetic modifiers that modify chromatin to change target gene expression. The third category of NUP98 fusions has neither the DNA binding nor chromatin remodeling domain.<ref name=":0">{{Cite journal|last=Mohanty|first=Sagarajit|date=2023-09|title=NUP98 Rearrangements in AML: Molecular Mechanisms and Clinical Implications|url=https://www.mdpi.com/2673-7523/3/3/11|journal=Onco|language=en|volume=3|issue=3|pages=147–164|doi=10.3390/onco3030011|issn=2673-7523}}</ref>  

Acute myeloid leukaemia (AML) with NUP98 rearrangement is characterized by chromosomal translocations involving NUP98 (nucleoporin 98 kDa) on chromosome 11p15.4 and various partner genes. (Reference WHO book). There are over 40 fusion partners which have been reported to date. NUP98 fusions can be categorized into three broad parts. The first category includes NUP98 fusions with transcription factors as partners, which can change the expression of target genes through DNA binding domains. The second category is NUP98 fusions with epigenetic modifiers that modify chromatin to change target gene expression. The third category of NUP98 fusions has neither the DNA binding nor chromatin remodeling domain.<ref name=":0">{{Cite journal|last=Mohanty|first=Sagarajit|date=2023-09|title=NUP98 Rearrangements in AML: Molecular Mechanisms and Clinical Implications|url=https://www.mdpi.com/2673-7523/3/3/11|journal=Onco|language=en|volume=3|issue=3|pages=147–164|doi=10.3390/onco3030011|issn=2673-7523}}</ref>  

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

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

No characteristic chromosomal gain or loss. However, trisomy 8 and chromosome 13 abnormalities may be observed.

No characteristic chromosomal gain or loss. However, trisomy 8 and chromosome 13 abnormalities may be observed.

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 or Other Global Mutational Patterns==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

!Chromosomal Pattern

!Chromosomal Pattern

!Diagnostic Significance (Yes, No or Unknown)

!Molecular Pathogenesis

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!Notes

!'''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>

Co-deletion of 1p and 18q

Co-deletion of 1p and 18q

|Yes

|<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).

|No

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

|No

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

|<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).

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

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==Gene Mutations (SNV / INDEL)==

==Gene Mutations (SNV/INDEL)==

FLT3-ITD and WT1 mutation are recurring events in NUP98::NSD1 and was also observed in some NUP98::HOXA9 AML patients.(R1). Loss of RB1 at 13q14 is particularly associated with NUP98::KDM5A  

FLT3-ITD and WT1 mutation are recurring events in NUP98::NSD1 and was also observed in some NUP98::HOXA9 AML patients.(R1). Loss of RB1 at 13q14 is particularly associated with NUP98::KDM5A  

{| class="wikitable"

{| class="wikitable"

==Epigenomic Alterations==

==Epigenomic Alterations==

Put your text here

Put your text here

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>

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>

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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|-

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

|<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> MAPK signaling

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

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

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|-

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

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

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

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

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

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

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|-

|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; 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> Histone modification, chromatin remodeling

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

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

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==Genetic Diagnostic Testing Methods==

==Genetic Diagnostic Testing Methods==

==Familial Forms==

==Familial Forms==

Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>

Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>

==Additional Information==

==Additional Information==

==Links==

==Links==

==References==

==References==

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>

<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.

 

Prior Author(s):

<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with NUP98 rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_NUP98_rearrangement</nowiki>.

<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with NUP98 rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_NUP98_rearrangement</nowiki>.

[[Category:HAEM5]]

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:DISEASE]]

[[Category:Diseases A]]

[[Category:Diseases A]]