<i>HMG-I/Y</i>, a New c-Myc Target Gene and Potential Oncogene

Wood, Lisa J.; Dolde, Christine; Xu, Yi; Maher, Joseph F.; Bunton, Tracie E.; Williams, John; Resar, Linda M.S.

doi:10.1128/mcb.20.15.5490-5502.2000

Cited by 169 publications

(239 citation statements)

References 95 publications

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“…[20][21][22][23][24][25][26][27][28][29][30][31][32] The putative oncogene, HMGIY (high mobility group protein isoforms I and Y), localized to 6p21 has been proposed to play a role in the development of a number of these neoplasms. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] An identical t(17;17)(q12;p13) was seen in two previous studies. 7,9 Interestingly, an inversion of chromosome 17 [inv(17)(p13q11.2-12)] involving similar breakpoints was observed in case 37 of the present study (Figure 3).…”

Section: Discussionmentioning

confidence: 80%

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

et al. 2004

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Aneurysmal bone cyst is a benign, cystic lesion of bone composed of blood-filled spaces separated by fibrous septa. Relatively few cases of aneurysmal bone cyst have been cytogenetically characterized, yet abnormalities of the short arm of chromosome 17 appear to be recurrent. In this study, conventional cytogenetic analysis of 43 aneurysmal bone cyst specimens from 38 patients over a 12-year period revealed clonal chromosomal abnormalities in 12 specimens. Karyotypic anomalies of 17p, including a complex translocation and inversion, were identified in eight of these 12 specimens. In an effort to further define the aberrant 17p breakpoint, fluorescence in situ hybridization (FISH) analyses were performed using a series of probe combinations spanning a 5.1 Mb region between the TP53 (17p13.1) and Miller-Dieker lissencephaly syndrome (17p13.3) gene loci. These studies revealed the critical breakpoint locus at 17p13.2, flanked proximally by an RP11-46I8, RP11-333E1, and RP11-457I18 bacterial artificial chromosome (BAC) probe cocktail and distally by an RP11-198F11 and RP11-115H24 BAC and RP5-1050D4 P1 artificial chromosome (PAC) probe cocktail. Overall, abnormalities of the 17p13.2 locus were identified by metaphase and/or interphase cell FISH analysis in 22 of 35 (63%) aneurysmal bone cyst specimens examined including 26 karyotypically normal specimens. These cytogenetic and molecular cytogenetic findings expand our knowledge of chromosomal alterations in aneurysmal bone cyst, further localize the critically involved 17p breakpoint, and provide an alternative approach (ie FISH) for detecting 17p abnormalities in nondividing cells of aneurysmal bone cysts. The latter could potentially be utilized as an adjunct in diagnostically challenging cases.

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Section: Discussionmentioning

confidence: 80%

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

et al. 2004

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“…This suggests that, in humans, AKNA gene lesions could be a determining risk factor for how neutrophilmediated inflammatory reactions resolve into acute syndromes and/or neoplastic disorders [59]. Although we make no parallel between AKNA and HMG proteins, we speculate that given the evidence of HMGA1 direct contribution to neoplastic transformation [60][61][62], the shared involvement in inflammation [54], and the linkage of SNP at human AKNA AT-hook domain with higher risk for cervical cancer [23], physiopathological cooperation is at least plausible.…”

Section: Discussionmentioning

confidence: 99%

Coordinate activation of inflammatory gene networks, alveolar destruction and neonatal death in AKNA deficient mice

Ortiz‐Quintero

Rangel

et al. 2011

Cell Res

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Gene expression can be regulated by chromatin modifiers, transcription factors and proteins that modulate DNA architecture. Among the latter, AT-hook transcription factors have emerged as multifaceted regulators that can activate or repress broad A/T-rich gene networks. Thus, alterations of AT-hook genes could affect the transcription of multiple genes causing global cell dysfunction. Here we report that targeted deletions of mouse AKNA, a hypothetical AT-hook-like transcription factor, sensitize mice to pathogen-induced inflammation and cause sudden neonatal death. Compared with wild-type littermates, AKNA KO mice appeared weak, failed to thrive and most died by postnatal day 10. Systemic inflammation, predominantly in the lungs, was accompanied by enhanced leukocyte infiltration and alveolar destruction. Cytologic, immunohistochemical and molecular analyses revealed CD11b + Gr1 + neutrophils as major tissue infiltrators, neutrophilic granule protein, cathelin-related antimicrobial peptide and S100A8/9 as neutrophil-specific chemoattracting factors, interleukin-1β and interferon-γ as proinflammatory mediators, and matrix metalloprotease 9 as a plausible proteolytic trigger of alveolar damage. AKNA KO bone marrow transplants in wildtype recipients reproduced the severe pathogen-induced reactions and confirmed the involvement of neutrophils in acute inflammation. Moreover, promoter/reporter experiments showed that AKNA could act as a gene repressor. Our results support the concept of coordinated pathway-specific gene regulation functions modulating the intensity of inflammatory responses, reveal neutrophils as prominent mediators of acute inflammation and suggest mechanisms underlying the triggering of acute and potentially fatal immune reactions.

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“…29 -32 In addition to these genes, many important regulators of cell cyclerelated events including centrosome separation/segregation (eg, ARK2), 33 kinetochore association (eg, CENF), 34 functional components of mitotic check points (eg, CENPE and TTK orMps1), 35,36 chromatin association and DNA replication (eg, HMG-I/Y, chromatin assembly factor-I (p150), DNA helicase and DHFR). [37][38][39] A group of genes that promotes G 2 /M transit or are expressed in the M phase of the cell cycle, including CYCLIN-A, CDC2, CDC25C, and SAK, 40 -42 were also up-regulated. These results suggest that t(14;18)-negative GCB-DLBCL is significantly more mitotically active than the t(14;18)-positive cases, and indicates that the two cytogenetic subsets have distinctive biological characteristics.…”

Section: Discussionmentioning

confidence: 99%

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

Iqbal

Sanger

Horsman

et al. 2004

The American Journal of Pathology

267

173

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Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DL-BCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32; q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14; 18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup. Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B cells with an annual incidence of ϳ25,000 cases in the United States. DLBCL is a heterogeneous entity both clinically and morphologically. We have recently shown by gene expression profiling that DLBCL can be classified into two major subgroups. 1 The germinal center B-cell-like (GCB) subgroup expresses genes characteristic of normal GC B cells and is associated with a good outcome after multiagent chemotherapy, whereas the activated B-cell-like (ABC) subgroup expresses genes characteristic of activated blood B cells and is associated with a poor clinical outcome. Nonetheless, considerable molecular heterogeneity exists within each subgroup. A small number of DLBCL cases are unclassifiable and do not express the GCB or ABC sig-

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HMG-I/Y, a New c-Myc Target Gene and Potential Oncogene

Cited by 169 publications

References 95 publications

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization

Coordinate activation of inflammatory gene networks, alveolar destruction and neonatal death in AKNA deficient mice

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

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