The PVT‐1 oncogene is a Myc protein target that is overexpressed in transformed cells

Carramusa, Letizia; Contino, Flavia; Ferro, Arianna; Minafra, Luigi; Perconti, Giovanni; Giallongo, Agata; Feo, Salvatore

doi:10.1002/jcp.21133

Cited by 134 publications

(111 citation statements)

References 24 publications

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“…Considering that gene amplification is common in cancer and often related to activation of specific genes and pathways with oncogenic properties (26), we studied cytogenetic bands or genes with high CN gain (log 2 ratio >3). The nonprotein coding plasmacytoma variant translocation (PVT1) gene was of interest because it is immediately downstream of the MYC gene and thought to be oncogenic (27,28), and PVT1-CHD7 fusions were found in the NCI-H2171 and LU-135 SCLC cell lines (29). In our aCGH study, PVT1 intragenic CN gain was observed (SI Appendix, Fig.…”

Section: Recurrent Copy Number Alterations In Pulmonary Neuroendocrinementioning

confidence: 83%

Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

Voortman

Lee

Killian

et al. 2010

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

120

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The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.carcinoid | cell line | gene dosage | small cell lung carcinoma | therapy

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Section: Recurrent Copy Number Alterations In Pulmonary Neuroendocrinementioning

confidence: 83%

Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

Voortman

Lee

Killian

et al. 2010

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

120

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“…For example, it is known that the neighboring gene PVT1 (8q24) is a transcriptional activator of MYC. 12 In secondary (post-irradiation) angiosarcomas, Mentzel et al 3 have shown MYC overexpression in all but one MYC-amplified tumor.…”

Section: Discussionmentioning

confidence: 99%

MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study

et al. 2014

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MYC, a proto-oncogene located on chromosome 8q24, is involved in the control of cell proliferation and differentiation. Previous studies have documented high-level MYC gene amplification and MYC overexpression by immunohistochemistry (IHC) in post-irradiation angiosarcomas, but not in primary cutaneous angiosarcoma (AS-C) or in other radiation-associated vascular proliferations, such as atypical vascular lesions. Prompted by our recent finding of MYC amplification in a primary hepatic AS, we analyzed a large number of wellcharacterized AS-C for MYC amplification and protein overexpression. Formalin-fixed, paraffin-embedded blocks from 38 AS-C were retrieved from our archives and were examined by IHC analysis and fluorescence in-situ hybridization (FISH), using a commercially available antibody and probe. For FISH analysis, the number of copies of MYC was compared with the control gene, CEN8 (MYC/CEN8 ratio). All cases occurred on sunexposed skin; no patient was known to have a history of therapeutic irradiation. Possible associations between survival and a wide variety of clinicopathological variables were evaluated using the log-rank test. By IHC analysis, MYC overexpression was present in 9/38 (24%) AS-C (2-3 þ : 6 cases, 16%; 1 þ : 3 cases, 8%). By FISH analysis, 2/5 (40%) informative cases with 2-3 þ immunostaining showed high-level gene amplification. One additional case with 3 þ immunostaining showed higher level aneusomy of chromosome 8 (5-8 MYC and CEN8). Two out of fourteen (14%) IHC-negative cases also carried MYC amplification (one high level and one lower level). Low copy number gain of chromosome 8 (3-5 MYC and CEN8) was observed in AS-C with or without MYC expression. MYC amplification and MYC protein overexpression were not correlated with clinical outcome. We have shown, for the first time, MYC gene amplification and protein overexpression in primary (non-radiation-associated) AS of the skin. MYC protein overexpression in cases lacking gene amplification likely reflects other mechanisms of MYC activation. The study of a larger number of AS-C showing MYC amplification may be necessary to determine whether the behavior of such cases differs from their more common non-amplified counterparts.

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“…In this translocation, the first exon/intron of PVT1 that includes miR-1204 is linked to exons 2 and 3 of MYC leading to high levels of expression of both miR-1204 and MYC in these MBs (Northcott et al 2012b). MiR-1204 has been implicated as a candidate oncogene in combination with MYC (Shtivelman and Bishop 1989;Carramusa et al 2007;Northcott et al 2012b).…”

Section: Microrna Regulation Of Mycmentioning

confidence: 99%

Role of MYC in Medulloblastoma

Roussel

Robinson

2013

Cold Spring Harbor Perspectives in Medicine

134

109

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Since its discovery as an oncogene carried by the avian acute leukemia virus MC29 in myelocytomatosis (Roussel et al. 1979) and its cloning (Vennstrom et al. 1982), c-MYC (MYC), as well as its paralogs MYCN and MYCL1, has been shown to play essential roles in cycling progenitor cells born from proliferating zones during embryonic development, and in all proliferating cells after birth. MYC deletion induces cell-cycle exit or cell death, depending on the cell type and milieu, whereas MYC and MYCN amplification or overexpression promotes cell proliferation and occurs in many cancers. Here, we review the relationship of MYC family proteins to the four molecularly distinct medulloblastoma subgroups, discuss the possible roles MYC plays in each of these subgroups and in the developing cells of the posterior fossa, and speculate on possible therapeutic strategies targeting MYC.

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The PVT‐1 oncogene is a Myc protein target that is overexpressed in transformed cells

Cited by 134 publications

References 24 publications

Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors

MYC amplification and overexpression in primary cutaneous angiosarcoma: a fluorescence in-situ hybridization and immunohistochemical study

Role of MYC in Medulloblastoma

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