Compendium of Cancer Genome Aberrations

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RUNX1 (view source)

Revision as of 14:48, 12 December 2023

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==Primary Author(s)*==
 
==Primary Author(s)*==
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Brian Davis, PhD
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Brian Davis, PhD, MindFull Informatics LLC
    
__TOC__
 
__TOC__
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==Cancer Category/Type==
 
==Cancer Category/Type==
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* '''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]'''
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*'''[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]'''
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'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_t(8;21)(q22;q22.1);_RUNX1-RUNX1T1 Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]'''
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'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_Mutated_RUNX1 Acute Myeloid Leukemia (AML) with Mutated RUNX1]'''
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--- '''[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_RUNX1::RUNX1T1_fusion Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]'''
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The frequency of ''RUNX1'' mutations is between 5-18% of all AML patients tested [3]. The most common chromosomal translocation is t(8;21)(q22;q22)resulting in RUNX1-RUNX1T1 fusion in ''de novo'' AML, at approximately 7% [2,6]. This translocation confers a favorable prognosis in AML and other neoplasms [2,5,6]. Another ''RUNX1'' alteration is the t(3;21)(q26;q22), in which the RUNT domain of ''RUNX1'' is fused to the entire ''EVI1'' gene.  This translocation is rarely found in patients diagnosed with ''de novo'' AML and is more common in those with therapy-related myelodysplastic syndrome (MDS)/AML [9].  Other mutations in ''RUNX1'' include deletions, missense, splicing, frameshift, and nonsense alterations (mostly loss-of-function or decreased function), and occur at a frequency of approximately 10% in AML patients [6]. These mutations are mechanistically distinct from the chromosomal translocations and confer a worse prognosis [2,5,6].
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--- '''[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_with_Mutated_RUNX1 Acute Myeloid Leukemia (AML) with Mutated RUNX1]'''
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The frequency of ''RUNX1'' mutations is between 5-18% of all AML patients tested [3]. The most common chromosomal translocation is t(8;21)(q22;q22) resulting in RUNX1-RUNX1T1 fusion in ''de novo'' AML, at approximately 7% [2,6].  This translocation confers a favorable prognosis in AML and other neoplasms [2,5,6].  Another ''RUNX1'' alteration is the t(3;21)(q26;q22), in which the RUNT domain of ''RUNX1'' is fused to the entire ''EVI1'' gene.  This translocation is rarely found in patients diagnosed with ''de novo'' AML and is more common in those with therapy-related myelodysplastic syndrome (MDS)/AML [9].  Other mutations in ''RUNX1'' include deletions, missense, splicing, frameshift, and nonsense alterations (mostly loss-of-function or decreased function), and occur at a frequency of approximately 10% in AML patients [6]. These mutations are mechanistically distinct from the chromosomal translocations and confer a worse prognosis [2,5,6].
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* '''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''
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*'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_Predisposition Myeloid Neoplasms with Germline Predisposition]'''
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--- '''[http://www.ccga.io/index.php/HAEM4:Myeloid_Neoplasms_with_Germline_RUNX1_Mutation Myeloid Neoplasms with Germline RUNX1 Mutation]'''
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*'''[http://www.ccga.io/index.php/Acute_lymphoblastic_leukaemia_(ALL) Acute Lymphocytic Leukemia (ALL)]'''
    
iAMP21 is an intrachromosomal amplification of chromosome 21, which includes the genes ''RUNX1'' and ''miR-802'' among others.  This amplification occurs in about 1.5-2% of all Acute Lymphocytic Leukemia cases tested and is associated with poor prognostication [5].  
 
iAMP21 is an intrachromosomal amplification of chromosome 21, which includes the genes ''RUNX1'' and ''miR-802'' among others.  This amplification occurs in about 1.5-2% of all Acute Lymphocytic Leukemia cases tested and is associated with poor prognostication [5].  
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* '''[http://www.ccga.io/index.php/T-ALL T-cell Acute Lymphocytic Leukemia (T-ALL)]'''
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*'''[http://www.ccga.io/index.php/T-ALL T-cell Acute Lymphocytic Leukemia (T-ALL)]'''
    
''RUNX1'' mutations have been described in 20% of patients with early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) [6].
 
''RUNX1'' mutations have been described in 20% of patients with early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) [6].
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* '''[http://www.ccga.io/index.php?title=B_lymphoblastic_leukaemia/lymphoma_with_t(12;21)(p13;q22);_TEL-AML1_(ETV6-RUNX1)_positive&redirect=no B-cell Acute Lymphocytic Leukemia (B-ALL)]'''
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*'''[http://www.ccga.io/index.php?title=B_lymphoblastic_leukaemia/lymphoma_with_t(12;21)(p13;q22);_TEL-AML1_(ETV6-RUNX1)_positive&redirect=no B-cell Acute Lymphocytic Leukemia (B-ALL)]'''
    
The most common chromosomal translocation is t(12;21)(p13;q22) resulting in ETV6-RUNX1 fusion in B-cell acute lymphocytic leukemia (B-ALL) [2].  This translocation occurs in 25% of Pediatric B-ALL but only 2% of Adult B-ALL [5, 6], and confers a favorable prognosis in B-ALL and other neoplasms [2,5,6].  iAMP21 is an intrachromosomal amplification of chromosome 21 which includes the genes ''RUNX1'' and ''miR-802'' among others.  This amplification occurs in about 2% of all B-cell Acute Lymphocytic Leukemia cases tested and is associated with poor prognostication [6].  
 
The most common chromosomal translocation is t(12;21)(p13;q22) resulting in ETV6-RUNX1 fusion in B-cell acute lymphocytic leukemia (B-ALL) [2].  This translocation occurs in 25% of Pediatric B-ALL but only 2% of Adult B-ALL [5, 6], and confers a favorable prognosis in B-ALL and other neoplasms [2,5,6].  iAMP21 is an intrachromosomal amplification of chromosome 21 which includes the genes ''RUNX1'' and ''miR-802'' among others.  This amplification occurs in about 2% of all B-cell Acute Lymphocytic Leukemia cases tested and is associated with poor prognostication [6].  
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* '''Chronic Myeloid Leukemia (CML)'''
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*'''Chronic Myeloid Leukemia (CML)'''
    
A number of simple mutations in ''RUNX1'' have been reported in CML patients, and these mutations may be in part responsible for progression from the chronic phase to blast crisis (BC) [7].
 
A number of simple mutations in ''RUNX1'' have been reported in CML patients, and these mutations may be in part responsible for progression from the chronic phase to blast crisis (BC) [7].
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* '''[http://www.ccga.io/index.php/MDS Myelodysplastic Syndrome (MDS)]'''
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*'''[http://www.ccga.io/index.php/MDS Myelodysplastic Syndrome (MDS)]'''
    
A high frequency (42%) of ''RUNX1'' mutations has been reported among radiation-associated and therapy-related Myelodysplastic Syndrome (MDS) patients [8].  
 
A high frequency (42%) of ''RUNX1'' mutations has been reported among radiation-associated and therapy-related Myelodysplastic Syndrome (MDS) patients [8].  
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* '''CCUS or ICUS'''
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*'''CCUS (Clonal cytopenia of undetermined significance) or ICUS (Idiopathic cytopenia of undetermined significance )'''
    
''RUNX1'' mutations are more common in clonal cytopenia of undetermined significance (CCUS) [2].
 
''RUNX1'' mutations are more common in clonal cytopenia of undetermined significance (CCUS) [2].
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* '''Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)'''
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*'''Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)'''
    
Germline mutations of ''RUNX1'' have been reported in the rare autosomal dominant Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) [8].
 
Germline mutations of ''RUNX1'' have been reported in the rare autosomal dominant Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) [8].
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{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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! Copy Number Loss   !! Copy Number Gain   !! LOH   !!   Loss-of-Function Mutation   !! Gain-of-Function Mutation !! Translocation/Fusion  
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!Copy Number Loss!!Copy Number Gain!!LOH!!Loss-of-Function Mutation!!Gain-of-Function Mutation!!Translocation/Fusion
 
|-
 
|-
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| ||   ||   || X ||   || X
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| || || ||X|| ||X
 
|}
 
|}
    
==Internal Pages==
 
==Internal Pages==
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[[Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]]
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'''[[HAEM5:Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion]]'''
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'''[[HAEM4:Acute Myeloid Leukemia (AML) with Mutated RUNX1]]'''
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[[Acute Myeloid Leukemia (AML) with Mutated RUNX1]]
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'''[[HAEM4:Myeloid Neoplasms with Germline RUNX1 Mutation]]'''
    
==External Links==
 
==External Links==
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'''[http://oncokb.org/#/gene/RUNX1 ''RUNX1'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
 
'''[http://oncokb.org/#/gene/RUNX1 ''RUNX1'' by OncoKB]''' - mutational landscape, mutation effect, variant classification
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'''[https://www.ncbi.nlm.nih.gov/gene/861 ''RUNX1'' by NCBI]''' - brief gene overview
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'''[https://www.ncbi.nlm.nih.gov/gene/861 ''RUNX1'' by NCBI Gene]''' - brief gene overview
    
'''[https://www.mycancergenome.org/content/gene/RUNX1/ ''RUNX1'' by My Cancer Genome]''' - brief gene overview
 
'''[https://www.mycancergenome.org/content/gene/RUNX1/ ''RUNX1'' by My Cancer Genome]''' - brief gene overview
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'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=RUNX1 ''RUNX1'' by GeneCards]''' - general gene information and summaries
 
'''[http://www.genecards.org/cgi-bin/carddisp.pl?gene=RUNX1 ''RUNX1'' by GeneCards]''' - general gene information and summaries
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'''[https://databases.lovd.nl/shared/genes/RUNX1 "RUNX1" by VOVD(3)]''' - Leiden Open Variation Database
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'''[http://www.omim.org/entry/151385 ''RUNX1'' by OMIM]''' - compendium of human genes and genetic phenotypes
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'''[https://databases.lovd.nl/shared/genes/RUNX1 ''RUNX1'' by LOVD(3)]''' - Leiden Open Variation Database
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'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=RUNX1 ''RUNX1'' by TICdb]''' - database of Translocation breakpoints In Cancer
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RUNX1 by LOVD3
    
==References==
 
==References==
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<references />
 
1. Trippier PC, (2017).  Small molecule inhibitors for acute myeloid leukemia: where is the field heading? Future Med Chem 13:1453-1456, PMID 28795593. doi: 10.4155/fmc-2017-0114.
 
1. Trippier PC, (2017).  Small molecule inhibitors for acute myeloid leukemia: where is the field heading? Future Med Chem 13:1453-1456, PMID 28795593. doi: 10.4155/fmc-2017-0114.
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9. 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. Revised 4th Edition. IARC Press: Lyon, France, p140-141.
 
9. 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. Revised 4th Edition. IARC Press: Lyon, France, p140-141.
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== Notes ==
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==Notes==
 
<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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<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 CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
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[[Category:Cancer Genes R]]
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