mercredi 30 mai 2012

Mutated genes in cancer (73) – RUNX1


In databases:

● Entrez ( 861 or RUNX1
● Ensembl ( ENSG00000159216
● UniProt ( Q01196
● GeneCards ( RUNX1
● HGNC ( 10471 or RUNX1

Gene locus:


Protein name:

Runt-related transcription factor 1

Protein Size:

453 amino acids; about 49 kDa


The protein encoded by RUNX1 is a transcription factor associated with acute myeloid leukemia (AML). It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα). RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. RUNX1 is thought to be involved in the development of normal hematopoiesis.

Cancer-related alterations:

Somatic RUNX1 mutations (deletion, insertion, point mutations) have been observed in tumors of haematopoietic/lymphoid tissue and CNS.  There are no mutational hot spots.
RUNX1 is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML).

Chromosomal alterations involving RUNX1 and leading to fusion genes are well-documented and have been associated with several types of leukemia.

ins(8;21)(q22;q22q22) leads to RUNX1-RUNX1T1 in AML
ins(21;8)(q22;q13q22) leads to RUNX1-RUNX1T1 in AML
ins(21;8)(q22;q21q22) leads to RUNX1-RUNX1T1 in AML
t(1;21)(p35;q22) leads to RUNX1-YTHDF2 in AML
t(1;21)(p36;q22) leads to RUNX1-PRDM16 in AMLt, MDS
t(1;21)(q21;q22) leads to RUNX1-ZNF687 in AML
t(2;21)(q11;q22) leads to RUNX1-AFF3 in T-ALL
t(3;21)(q26;q22) leads to RUNX1-RPL22P1 in CML, AML, MDS
t(3;21)(q26;q22) leads to RUNX1-MDS1 in AMLt, MDSt
t(3;21)(q26;q22) leads to RUNX1-EVI1 in CML, MDSt, AML, AMLt
t(4;21)(q31;q22) leads to RUNX1-SH3D19 in AML
t(7;21)(p22;q22) leads to RUNX1-USP42 in AML
t(8;21)(q21-q22;q22) leads to RUNX1-RUNX1T1 in AML
t(8;21)(q23;q22) leads to ZFPM2-RUNX1 in RAEB
t(8;21)(q24;q22) leads to RUNX1-TRPS1 in T-ALL, AML
t(11;21)(q13;q22) leads to MACROD1-RUNX in AML, CML, MDS
t(12;21)(p13;q22) leads to ETV6-RUNX1  in B-ALL
t(12;21)(q12;q22) leads to RUNX1-CPNE8 in AML
t(16;21)(q24;q22) leads to RUNX1-CBFA2T3 in MDS, AML, AMLt
t(X;21)(p22;q22) leads to RUNX1-PRDX4 in AML

Abbreviations: AML: acute myeloid leukemia; AMLt: acute myelogenous leukemia, primarily treatment associated; MDS: myelodysplastic syndrome; T-ALL: T-cell acute lymphocytic leukemia; CML: chronic myeloid leukemia; MDSt: myelodysplastic syndrome, primarily treatment associated; RAEB: refractory anemia with excess blasts; B-ALL: B-cell acute lymphocytic leukaemia.

RUNX1 genetic alterations are the cause of familial platelet disorder with associated myeloid malignancy (FPD-AML or FPDMM), which is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.

References (open access) :

Familial myelodysplastic syndromes - a review of the literature. Liew E, Owen CJ. Haematologica. 2011 May 23

Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, Gelsi-Boyer V, Mozziconacci MJ. BMC Cancer. 2010 Aug 2;10:401.

RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia. Edwards H, Xie C, LaFiura KM, Dombkowski AA, Buck SA, Boerner JL, Taub JW, Matherly LH, Ge Y. Blood. 2009 Sep 24;114(13):2744-52.

Integrative analysis of RUNX1 downstream pathways and target genes. Michaud J, Simpson KM, Escher R, Buchet-Poyau K, Beissbarth T, Carmichael C, Ritchie ME, Schütz F, Cannon P, Liu M, Shen X, Ito Y, Raskind WH, Horwitz MS, Osato M, Turner DR, Speed TP, Kavallaris M, Smyth GK, Scott HS. BMC Genomics. 2008 Jul 31;9:363.

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