Difference between revisions of "RUNX1T1"

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search
[unchecked revision][unchecked revision]
 
(11 intermediate revisions by 2 users not shown)
Line 11: Line 11:
 
==Genomic Location==
 
==Genomic Location==
  
'''Cytoband:''' 8q21.3
+
'''Cytoband:''' 8q21.3 (previously located at 8q22, as represented in the name of one of the WHO disease categories of AML)
  
 
'''Genomic Coordinates:'''  
 
'''Genomic Coordinates:'''  
Line 21: Line 21:
 
==Cancer Category/Type==
 
==Cancer Category/Type==
  
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]'''
+
'''[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/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]'''
+
'''[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]'''
  
The t(8;21)(q22;q22) (RUNXT1, RUNX1) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7].  The translocation t(8;21)(q22;q22.1);_RUNX1-RUNX1T1 produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 (RUNX1) gene fused to the 3'-region of the RUNX1T1 gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.
+
The t(8;21)(q22;q22.1), resulting in fusion of ''RUNXT1'' and ''RUNX1'', is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7].  The t(8;21)(q22;q22.1) produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 (''RUNX1'') gene fused to the 3'-region of the ''RUNX1T1'' gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.
  
 
==Gene Overview==
 
==Gene Overview==
  
The RUNX1T1 gene is a member of the human myeloid translocation genes (MTGs).  The nuclear MTGs can mediate the formation of complex protein networks among nuclear corepressors (for example Sin3a, N-CoR, SMRT), chromatin-modifying enzymes (for example histone deacetylases), and DNA-binding transcription factors. Repression at target genes by MTG protein complexes is probably required for gene regulation during development and differentiation. Alterations in these genes can disrupt gene regulatory protein networks and can cause of cancers and neurodegeneration [8]  The translocation t(8;21)(q22;q22.1);_RUNX1-RUNX1T1 produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 (RUNX1) gene fused to the 3'-region of the RUNX1T1 gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.
+
''RUNX1T1'' is a member of the human myeloid translocation genes (MTGs).  The nuclear MTGs can mediate the formation of complex protein networks among nuclear corepressors (for example Sin3a, N-CoR, SMRT), chromatin-modifying enzymes (for example histone deacetylases), and DNA-binding transcription factors. Repression at target genes by MTG protein complexes is probably required for gene regulation during development and differentiation. Alterations in these genes can disrupt gene regulatory protein networks and can cause of cancers and neurodegeneration [8]. The RUNX1-RUNX1T1 chimeric protein resulting from the t(8;21)(q22;q22.1) is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.
  
 
==Common Alteration Types==
 
==Common Alteration Types==
  
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_with_t(8;21)(q22;q22.1);_RUNX1-RUNX1T1 Acute Myeloid Leukemia (AML)]'''
+
'''[http://www.ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_RUNX1::RUNX1T1_fusion Acute Myeloid Leukemia (AML)]'''
  
The t(8;21)(q22;q22) (RUNXT1, RUNX1) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7].  
+
The t(8;21)(q22;q22), resulting in RUNXT1-RUNX1 fusion, is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7].
  
 
{| 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
 
|-
 
|-
| || || || || || X
+
| || || || || ||X
 
|}
 
|}
  
 
==Internal Pages==
 
==Internal Pages==
  
'''[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]'''
+
'''[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]'''
  
 
==External Links==
 
==External Links==
Line 67: Line 69:
  
 
'''[https://www.ncbi.nlm.nih.gov/gene/862 RUNX1T1 by NCBI Gene]''' - general gene information and summaries
 
'''[https://www.ncbi.nlm.nih.gov/gene/862 RUNX1T1 by NCBI Gene]''' - general gene information and summaries
 +
 +
'''[http://www.omim.org/entry/133435 ''RUNX1T1'' by OMIM]''' - compendium of human genes and genetic phenotypes
 +
 +
'''[https://databases.lovd.nl/shared/genes/RUNX1T1 ''RUNX1T1'' by LOVD(3)]''' - Leiden Open Variation Database
 +
 +
'''[http://www.unav.es/genetica/TICdb/results.php?hgnc=RUNX1T1 ''RUNX1T1'' by TICdb]''' - database of Translocation breakpoints In Cancer
  
 
==References==
 
==References==
  
1. Trippier, P. C. (2017). Small molecule inhibitors for acute myeloid leukemia: where is the field heading? Future Med. Chem. 13:1453-1456PMID 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.
  
2. Bellissimo, D.C. and Speck, N. A. (2017). RUNX1 Mutations in Inherited and Sporadic Leukemia. Front Cell Dev. Biol. 5: 111 PMID 29326930 10.3389/fcell.2017.00111
+
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, et al. (2017).  Molecular Mutations and Their Cooccurrences in Cytogenetically Normal Acute Myeloid Leukemia. Stem Cells Int. 2017:6962379   PMID 28197208 doi: 10.1155/2017/6962379
+
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.
  
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.
+
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. Post SM. et al. (2015). Biology of Adult Myelocytic Leukemia and Myeldysplasia 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.
+
5. Post SM, et al., (2015). Biology of adult myelocytic leukemia and myelodysplasia 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.
+
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. 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.
 
7. 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.
  
8. Rossetti S. et al. (2004). The MTG proteins: chromatin repression players with a passion for networking. Genomics 84:1-9PMID: 15203199 DOI 10.1016/j.ygeno.2004.02.011
+
8. Rossetti S, et al., (2004). The MTG proteins: chromatin repression players with a passion for networking. Genomics 84:1-9, PMID 15203199. DOI 10.1016/j.ygeno.2004.02.011.
  
== Notes ==
+
==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]]

Latest revision as of 14:48, 12 December 2023

Primary Author(s)*

Brian Davis, PhD

Synonyms

"RUNX1 translocation partner 1"; "Cyclin-D-Related Protein"; CDR; "Eight Twenty One Protein"; ETO; "Myeloid Translocation Gene On 8q22"; MTG8; "Acute Myelogenous Leukemia 1 Translocation 1"; AML1T1; "Zinc Finger MYND Domain-Containing Protein 2"; ZMYND2; "Core-Binding Factor, Runt Domain, Alpha Subunit 2; Translocated To, 1; Cyclin D-Related"; CBFA2T1; AML1-MTG8

Genomic Location

Cytoband: 8q21.3 (previously located at 8q22, as represented in the name of one of the WHO disease categories of AML)

Genomic Coordinates:

chr8:91,954,967-92,103,286(GRCh38/hg38)

chr8:92,967,195-93,115,514(GRCh37/hg19)

Cancer Category/Type

Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms

Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1

The t(8;21)(q22;q22.1), resulting in fusion of RUNXT1 and RUNX1, is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7]. The t(8;21)(q22;q22.1) produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 (RUNX1) gene fused to the 3'-region of the RUNX1T1 gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.

Gene Overview

RUNX1T1 is a member of the human myeloid translocation genes (MTGs). The nuclear MTGs can mediate the formation of complex protein networks among nuclear corepressors (for example Sin3a, N-CoR, SMRT), chromatin-modifying enzymes (for example histone deacetylases), and DNA-binding transcription factors. Repression at target genes by MTG protein complexes is probably required for gene regulation during development and differentiation. Alterations in these genes can disrupt gene regulatory protein networks and can cause of cancers and neurodegeneration [8]. The RUNX1-RUNX1T1 chimeric protein resulting from the t(8;21)(q22;q22.1) is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation.

Common Alteration Types

Acute Myeloid Leukemia (AML)

The t(8;21)(q22;q22), resulting in RUNXT1-RUNX1 fusion, is one of the most frequent karyotypic abnormalities in acute myeloid leukemia with a reported incidence of 7% [5,7].

Copy Number Loss Copy Number Gain LOH Loss-of-Function Mutation Gain-of-Function Mutation Translocation/Fusion
X

Internal Pages

Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms

Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1

External Links

RUNX1T1 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information

RUNX1T1 by COSMIC - sequence information, expression, catalogue of mutations

RUNX1T1 by St. Jude ProteinPaint mutational landscape and matched expression data.

RUNX1T1 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs

RUNX1T1 by My Cancer Genome - brief gene overview

RUNX1T1 by UniProt - protein and molecular structure and function

RUNX1T1 by Pfam - gene and protein structure and function information

RUNX1T1 by GeneCards - general gene information and summaries

RUNX1T1 by NCBI Gene - general gene information and summaries

RUNX1T1 by OMIM - compendium of human genes and genetic phenotypes

RUNX1T1 by LOVD(3) - Leiden Open Variation Database

RUNX1T1 by TICdb - database of Translocation breakpoints In Cancer

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.

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. Post SM, et al., (2015). Biology of adult myelocytic leukemia and myelodysplasia 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. 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.

8. Rossetti S, et al., (2004). The MTG proteins: chromatin repression players with a passion for networking. Genomics 84:1-9, PMID 15203199. DOI 10.1016/j.ygeno.2004.02.011.

Notes

*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.