The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22→q24

Chaganti, R. S. K.; Balazs, Iván; Jhanwar, Suresh C.; Murty, Vundavalli V.; Koduru, Prasad; Grzeschik, K.-H.; Stavnezer, Ed

doi:10.1159/000132318

Cited by 42 publications

(16 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Ski and Sno oncogenes that were transduced by avian leukemia viruses contain regions of homology to myosin heavy chains (8,37,42). Both of these oncogenes associate with mSin3A and are capable of repressing transcription and/or acting as corepressors (38).…”

Section: Discussionmentioning

confidence: 99%

The inv(16) Fusion Protein Associates with Corepressors via a Smooth Muscle Myosin Heavy-Chain Domain

Durst¹,

Lutterbach²,

Kummalue

et al. 2003

Molecular and Cellular Biology

148

138

View full text Add to dashboard Cite

Inversion (16) is one of the most frequent chromosomal translocations found in acute myeloid leukemia (AML), occurring in over 8% of AML cases. This translocation results in a protein product that fuses the first 165 amino acids of core binding factor ␤ to the coiled-coil region of a smooth muscle myosin heavy chain (CBF␤/SMMHC). CBF␤ interacts with AML1 to form a heterodimer that binds DNA; this interaction increases the affinity of AML1 for DNA. The CBF␤/SMMHC fusion protein cooperates with AML1 to repress the transcription of AML1-regulated genes. We show that CBF␤/SMMHC contains a repression domain in the C-terminal 163 amino acids of the SMMHC region that is required for inv(16)-mediated transcriptional repression. This minimal repression domain is sufficient for the association of CBF␤/SMMHC with the mSin3A corepressor. In addition, the inv(16) fusion protein specifically associates with histone deacetylase 8 (HDAC8). inv(16)-mediated repression is sensitive to HDAC inhibitors. We propose a model whereby the inv(16) fusion protein associates with AML1 to convert AML1 into a constitutive transcriptional repressor.Human acute leukemias often arise from chromosomal translocations targeting regulatory genes that affect cell growth, differentiation, and apoptosis (30). These translocations often fuse transcription factors to other proteins resulting in oncogenic chimeric proteins. inv (16) is found in approximately 8% of acute myeloid leukemia (AML) cases (35), making it one of the most frequent translocations in AML. inv(16) fuses the first 165 amino acids (aa) of core binding factor ␤ (CBF␤) to the C-terminal coiled-coil region of a smooth muscle myosin heavy chain (SMMHC [the gene name is MYH11]) (28). CBF␤ interacts with the AML1 (also known as RUNX1) transcription factor to increase the affinity of AML1 for DNA (15,40,47) and to stimulate the ability of AML1 to either activate or repress transcription (22,32). Both components of the CBF␤-AML1 transcription factor complex are disrupted by chromosomal translocations. The translocations that target AML1 include t(8;21) and t(12;21) that result in the leukemogenic fusion proteins AML1/ETO and TEL/AML1 (10, 16).The CBF␤-AML1 complex regulates genes encoding cytokines and their receptors, genes involved in differentiation such as T-cell receptors, neutrophil peptide 3, and myeloperoxidase as well as the p14 ARF tumor suppressor (4,12,14,27,36,39,43,46,52). Furthermore, CBF␤/SMMHC slows the cell cycle transition from G 1 to S in hematopoietic cells; thus, cell cycle regulatory genes such as cdk4 may also be targeted by this complex (5).Animal studies indicate that CBF␤ and AML1 are required for hematopoiesis. CBF␤ and AML-1 knockout mice share a phenotype; these mice lack fetal liver hematopoiesis and are embryonic lethal at embryonic day 12.5 (e12.5) to e13.5 (41,49). A similar phenotype is observed in mice expressing CBF␤/ SMMHC from a "knocked-in" CBFB-MYH11 gene (7), suggesting that inv(16) creates a dominant repressor of AML1-and CBF␤-regulated genes. Chimer...

show abstract

Section: Discussionmentioning

confidence: 99%

The inv(16) Fusion Protein Associates with Corepressors via a Smooth Muscle Myosin Heavy-Chain Domain

Durst¹,

Lutterbach²,

Kummalue

et al. 2003

Molecular and Cellular Biology

148

138

View full text Add to dashboard Cite

show abstract

“…34 Several potentially important growth promoting genes have been mapped to 1q. [35][36][37][38][39][40][41][42] Because all cases with 1q aberrations showed gains of large parts of 1q, no minimal overlapping region could be defined.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Genetic Aberrations in Thymoma and Thymic Carcinoma

Zettl

Ströbel

Wagner

et al. 2000

The American Journal of Pathology

159

140

View full text Add to dashboard Cite

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (welldifferentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma. 1 classification, several types of thymomas are distinguished based on histological criteria: 1) type A thymomas (also called medullary or spindle-cell thymoma); 2) type AB thymomas (also called mixed thymoma); 3) type B thymomas which are subclassified as type B1 thymomas (also called lymphocyte-rich thymoma, lymphocytic thymoma, predominantly cortical thymoma, or organoid thymoma), type B2 thymomas (also called cortical thymoma) and type B3 thymomas (also called epithelial, atypical, or squamoid thymoma or well-differentiated thymic carcinoma, respectively) and; 4) type C thymomas (thymic carcinomas) which exhibit morphological similarities to corresponding neoplasms in organs other than the thymus (eg, primary thymic squamous cell carcinoma).

show abstract

“…The SKI, TRK and S100 tumor progression and metastasis genes, as well as BLC9 gene cloned from a translocation 1;14 in B cell acute lymphoblastic leukemia are localized within the region of 1q duplication. [31][32][33][34] Future investigations are warranted to see if any of these gene or other genes are altered in BL due to partial 1q duplications.…”

Section: Figurementioning

confidence: 99%

Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma

2001

View full text Add to dashboard Cite

In this study, CA46 and ST486, two Epstein-Barr (EBV) negative cell lines derived from sporadic BL, were analyzed by multicolor spectral karyotyping, G-banding, fluorescence in situ hybridization with single-copy gene probes, and comparative genomic hybridization (CGH). In addition to reciprocal t(8;14)(q24;q32) translocation involving c-myc and IgH loci, we identified a t(7;8;14)(q11.2;q24;q32) translocation in CA 46 cells and t(8;14;18)(q24;q32;q23) in ST486 cells. Both rearrangements were not previously described in BL and resulted in transposition of myc sequences in a new genomic configuration. Several DNA imbalances mapped by CGH at the same sites in both lines, may reflect recurrent genomic changes that are relevant to pathogenesis of BL. We tested the tumorigeni-

show abstract

The cellular homologue of the transforming gene of SKV avian retrovirus maps to human chromosome region 1q22→q24

Cited by 42 publications

References 9 publications

The inv(16) Fusion Protein Associates with Corepressors via a Smooth Muscle Myosin Heavy-Chain Domain

The inv(16) Fusion Protein Associates with Corepressors via a Smooth Muscle Myosin Heavy-Chain Domain

Recurrent Genetic Aberrations in Thymoma and Thymic Carcinoma

Novel genomic imbalances and chromosome translocations involving c-myc gene in Burkitt's lymphoma

Contact Info

Product

Resources

About