Differential Expression of the Translocated and the Untranslocated c-
            <i>myc</i>
            Oncogene in Burkitt Lymphoma

Ar-Rushdi, Abbas; Nishikura, Kazuko; Erikson, Jan; Watt, Rosemary; Rovera, Giovanni; Croce, Carlo M.

doi:10.1126/science.6414084

Cited by 319 publications

(144 citation statements)

References 18 publications

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“…Although MiT factor expression has not been carefully examined or reported, it is plausible that dysregulation of a normally tightly regulated promoter may result in mistimed transcription factor activity. With striking similarities to TFEB͞TFE3, this type of dysregulation is well known for Myc, another bHLH-LZ transcription factor, when it is juxtaposed to the Ig heavy chain enhancer by the t(8;14)(q24;q32) in Burkitt's lymphoma (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

Davis

Hsi

Arroyo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

227

173

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MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the ORF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms.M ITF, TFE3, TFEB, and TFEC are closely related basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factors (1-8) that may homo-or heterodimerize in all combinations to bind DNA (9). These factors share sequence homology in their DNA-contacting basic domains (10), as well as activation domains, and recognize identical DNA sequences (9), suggesting that they may regulate similar downstream targets. Genetic and biochemical studies have revealed functional overlap of MiT activity in certain developmental lineages. Specifically, use of knockout mice by Jenkins and colleagues (8) has elegantly demonstrated that, whereas mutation of either Mitf or TFE3 in mice does not disrupt osteoclast development, mutation of both genes or presence of a dominant-negative allele produces severe osteopetrosis. Homozygous mutation of MITF in the mouse is particularly devastating to the melanocyte lineage, resulting in failure of melanocyte development (5). In humans, Mitf haploinsufficiency results in type IIa Waardenburg syndrome (11). Mice homozygous null for TFE3 or TFEC had no recognized abnormalities (8), but TFEB nulls exhibited embryonic lethality associated with placental vascular defects (12). In addition, Mitf and TFE3 have been found to undergo identical modifications after cytokine stimulation (13), and MITF has been shown to directly regulate BCL2, a key apoptotic regulator, in a manner important for melanocyte and melanoma surv...

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Section: Discussionmentioning

confidence: 99%

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

Davis

Hsi

Arroyo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

227

173

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“…Mutations of the gene and alterations in its expression are implicated in several malignancies, including Acute Myelogenous Luekemia and pre-leukemia (Reddy and Sulcova, 1997). Translocations involving c-myc are implicated in Burkitt's Lymphoma (Dalla-Favera et al, 1982;Taub et al, 1982;Ar-Rushdi et al, 1983) and altered translation of c-myc may be involved in the genesis of Bloom's Syndrome (West et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of Myc1 and Myc2 isoforms in cells transformed by eIF4E: evidence for internal ribosome repositioning in the human c-myc 5′UTR

1999

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“…Ten micrograms of DNA from each sample was digested with the appropriate restriction endonuclease and examined by Southern blotting. Oncogene amplification was detected with the pRyc 7.4 probe for the MYC proto-oncogene mapped on 8q24 (Rushdi et al, 1983) and the pMAC 117 probe for the ERBB2 gene located on 17ql1.2-ql2 (no. 53408; American Type Culture Collection, Rockville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

Driouch

Mh²,

Beuzelin³

et al. 1997

Br J Cancer

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Summary To determine the relationship between breast cancer progression and gene amplification, we screened 62 distant metastases and 122 primary breast tumours for the amplification of the proto-oncogenes MYC and ERBB2 and the 11 ql 3 chromosomal region. Surprisingly, solid metastases showed an absence of gene amplification. These results suggest that the amplification of the proto-oncogenes MYC and ERBB2 and the 11 ql 3 chromosomal region seem to be involved mainly in the genesis of the primary breast tumour rather than its progression.Keywords: breast cancer; relapse; MYC; ERBB2, 11q13 region Breast cancer is the most common malignancy in women; one in nine Caucasian women are likely to develop breast cancer in their lifetime. Cancer progression can be divided into two major processes: primary site tumorigenesis and metastasis. Metastases are the main cause of death from cancer. Both genetic and epigenetic events may be involved in the process by which individual cells acquire the characteristics required for invasion, dissemination, survival and growth at the metastatic site. Cells have a genetically determined metastatic potential (Liotta et al, 1991). While tumorigenesis is known to involve multiple genetic alterations (Bishop, 1991), the situation is probably far more complex in the case of metastases.Breast cancer results from early and/or late mutational events. Constitutional mutations in susceptibility genes (BRCAI, BRCA2, TP53, etc.) confer a predisposition to familial breast cancer. Sporadic breast cancer occurs through an accumulation of somatic mutations, i.e. amplifications of proto-oncogenes (MYC and ERBB2) and chromosomal band 1 q13, mutations of TP53 and loss of heterozygosity (LOH) of chromosomes and chromosome arms 1, 3p, 6q, 7q, 8p, 11, 13q, 16q, 17, 18q and 22q (Bieche and Lidereau, 1995).If alterations of specific genes are associated with the invasive process, they would probably be more frequently altered in metastases than in primary tumours. Brison (1993) reviewed several studies on different primary human tumours at different stages and suggested that proto-oncogene amplifications are probably late events in tumour progression. However, it is not yet known whether specific chromosomal regions are involved in invasive breast carcinoma because of a lack of screening studies for genetic alterations in secondary events, in particular distant metastases. MATERIALS AND METHODSHere we investigated the role of genetic amplifications in the acquisition of metastatic potential by means of restriction Torloni, 1981). The tumours were mostly invasive (85%); 40% of them were grade II and 40% were grade III. A third of the tumours did not show any lymph node metastases (N-). Primary tumours and matching pleural effusions were available from 12 patients. None of the 122 patients had undergone radiation therapy or chemotherapy before primary surgery. Patients whose metastases were sampled had undergone different adjuvant therapies. The median time to diagnosis of the distant metastases after prima...

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Differential Expression of the Translocated and the Untranslocated c- myc Oncogene in Burkitt Lymphoma

Cited by 319 publications

References 18 publications

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation

Differential expression of Myc1 and Myc2 isoforms in cells transformed by eIF4E: evidence for internal ribosome repositioning in the human c-myc 5′UTR

Classical gene amplifications in human breast cancer are not associated with distant solid metastases

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