Autochecked users, Comment administrators, Editors, Interface administrators, Reviewers, Suppressors, Administrators, Widget editors
1,874
edits
Changes
no edit summary
==Primary Author(s)*==
==Primary Author(s)*==
Brian Davis, PhD
Brian Davis, PhD, MindFull Informatics LLC
__TOC__
__TOC__
==Synonyms==
==Synonyms==
"Runt-related transcription factor 1"; "Acute Myeloid Leukemia 1 Protein"; AML1; ; "Core-Binding Factor Subunit Alpha-2"; CBF2 alpha; CBFA2; "Polyomavirus Enhancer-Binding Protein 2 Alpha B Subunit"; PEBP2aB; PEBP2 alpha; EVI-1; AML1-EVI-1; AMLCR1;
"Runt-related transcription factor 1"; "Acute Myeloid Leukemia 1 Protein"; AML1; "Core-Binding Factor Subunit Alpha-2"; CBF2 alpha; CBFA2; "Polyomavirus Enhancer-Binding Protein 2 Alpha B Subunit"; PEBP2aB; PEBP2 alpha; EVI-1; AML1-EVI-1; AMLCR1
==Genomic Location==
==Genomic Location==
'''Cytoband:''' Put your text here. EXAMPLE: 17p13.1
'''Cytoband:''' 21q22.12
'''Genomic Coordinates:'''
'''Genomic Coordinates:'''
chr21:36,160,098-37,376,965 [hg19]
chr21:34,787,801-36,004,667 [hg38]
==Cancer Category/Type==
*'''[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]'''
--- '''[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]'''
--- '''[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_with_Mutated_RUNX1 Acute Myeloid Leukemia (AML) with Mutated RUNX1]'''
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].
*'''[http://www.ccga.io/index.php/Myeloid_Neoplasms_with_Germline_Predisposition Myeloid Neoplasms with Germline Predisposition]'''
--- '''[http://www.ccga.io/index.php/HAEM4:Myeloid_Neoplasms_with_Germline_RUNX1_Mutation Myeloid Neoplasms with Germline RUNX1 Mutation]'''
*'''[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].
*'''[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].
*'''[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].
*'''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].
*'''[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].
*'''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].
*'''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].
==Gene Overview==
==Gene Overview==
The protein encoded by ''RUNX1'' can bind the protein encoded by ''CBFB'' to form "Core Binding Factor", a hetero-dimeric transcription factor which regulates a number of genes responsible for hematopoiesis and osteogenesis [2]. Runx1 protein can bind to DNA as a monomer through the Runt domain within the Runx1 protein. ''RUNX1'' is the most frequent target for chromosomal translocation in leukemia [1]. Alterations of ''RUNX1'' are typically loss-of-function or decreased function, and are considered "secondary driver mutations" (disease progression) in sporadic leukemias [2]; however, germline ''RUNX1'' mutations contribute to a lifetime risk for myeloid malignancy of about 44% [2]. ''RUNX1'' mutations (loss-of-function or decreased function) have been associated with decreased P53 activity and increased DNA repair defects and increased inflammation [2]. ''RUNX1'' mutations are associated with gene mutations in ''ASXL1'', ''MLLPTD'', and ''IDH1''/''IDH2'', but and are mutually exclusive with ''NPM1'' mutations [3]. Non-complex ''RUNX1'' mutations were found to be associated with resistance to chemotherapy, decreased disease free survival (DFS), event free survival (EFS) and overall survival (OS) [3].
==Common Alteration Types==
==Common Alteration Types==
'''Acute Myeloid Leukemia (AML);''' t(8;21)(q22;q22) resulting in RUNX1-RUNX1T1 fusion
'''B-cell Acute Lymphocytic Leukemia (B-ALL);''' t(12;21)(p13;q22) resulting in ETV6-RUNX1 fusion
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
!Copy Number Loss!!Copy Number Gain!!LOH!!Loss-of-Function Mutation!!Gain-of-Function Mutation!!Translocation/Fusion
|-
|-
| EXAMPLE: X ||EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X || EXAMPLE: X
| || || ||X|| ||X
|}
|}
==Internal Pages==
==Internal Pages==
'''[[HAEM5:Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion]]'''
'''[[HAEM4:Acute Myeloid Leukemia (AML) with Mutated RUNX1]]'''
'''[[HAEM4:Myeloid Neoplasms with Germline RUNX1 Mutation]]'''
==External Links==
'''[http://atlasgeneticsoncology.org/Genes/AML1ID52.html ''RUNX1'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[http://atlasgeneticsoncology.org/Genes/AML1ID52.html ''RUNX1'' by Atlas of Genetics and Cytogenetics in Oncology and Haematology]''' - detailed gene information
'''[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
'''[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
'''[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
'''[http://www.omim.org/entry/151385 ''RUNX1'' by OMIM]''' - compendium of human genes and genetic phenotypes
'''[https://databases.lovd.nl/shared/genes/RUNX1 ''RUNX1'' by LOVD(3)]''' - Leiden Open Variation Database
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=RUNX1 ''RUNX1'' by TICdb]''' - database of Translocation breakpoints In Cancer
RUNX1 by LOVD3
==References==
==References==
<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.
2. Bellissimo DC and Speck NA, (2017). RUNX1 mutations in inherited and sporadic leukemia. Front Cell Dev Biol 5:111, PMID 29326930. 10.3389/fcell.2017.00111.
3. Wang M, et al., (2017). Molecular mutations and their cooccurrences in cytogenetically normal acute myeloid leukemia. Stem Cells Int 6962379, PMID 28197208. doi: 10.1155/2017/6962379.
== Notes ==
4. Kamikubo Y, (2018). Genetic compensation of RUNX family transcription factors in leukemia. Cancer Sci (online version ahead of publication), PMID 29883054. doi.org/10.1111/cas.13664.
5. Schafer ES, et al., (2015). Molecular genetics of acute lymphoblastic leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
6. Taylor J, et al., (2017). Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood 130:410-423, PMID 28600336. doi: 10.1182/blood-2017-02-734541.
7. Zhao LJ, et al., (2012). Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood 119:2873-2882, PMID 22318203. DOI 10.1182/blood-2011-08-370981.
8. Harada H, et al., (2004). High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood 103:2316-2324, PMID 14615365. DOI: 10.1182/blood-2003-09-3074.
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.
==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.
[[Category:Cancer Genes R]]