The results suggest that partial hypomethylation of the c-myc gene third exon is associated with cell proliferation, and that deregulation of proliferation may be linked to the high levels of hypomethylation, presumably involving both copies of the gene in some cells, which occur at a relatively early stage in neoplastic progression.
These data indicate that HPV genomes are preferentially integrated near myc genes in invasive genital cancers and support the hypothesis that integration plays a part in tumor progression via an activation of cellular oncogenes.
Amplification of the myc gene proved to occur during a late stage of tumor progression and is not an early initiating event resulting from the direct action of radiation on target cells.
Amplification and/or overexpression of the c-myc gene were frequently observed in advanced-stage cervical cancers and were shown to be associated with tumor progression.
This in vivo rearrangement of the c-myc gene specific to tumor cells may represent one mechanism of activation of a protooncogene during tumorigenesis or tumor progression in human cancer.
This finding implies independent amplification events and supports the idea that the amplification of myc genes is probably a secondary event correlated with tumor progression.
A correlation was found between loss of heterozygosity on chromosome 1p32-pter and amplification of the MYC (formerly c-myc) protooncogene (P = 0.003), suggesting that these two genetic events may collaborate during tumor progression in human breast cancer.
Translocations involving an overexpressed c-myc gene are also found in AIDS-associated lymphoma or in T cell leukaemias, or they develop during tumour progression of a low grade B cell malignancy into a high grade B cell tumour in an additional cytogenetic change.
Candidate tumor suppressor genes and oncogenes affected by this trio of consistent changes include the c-myc gene on chromosome 8q24, the RB gene at 13q14, and potentially multiple novel genes on the short arm of chromosome 8, with a gene located more proximally potentially involved in tumor initiation and a gene or genes located more distally involved in tumor progression.
Some abnormalities, such as those involving chromosomes 1, 6, and 17, >4-6 clonal markers/cell, and rearrangements of c-MYC and TP53, have prognostic significance while others, such as trisomies 7, 12, 18, and X, are associated with tumor progression but their influence on overall survival is uncertain.
In multivariate analysis, p53 accumulation was found to be an independent predictor of tumor progression (p = 0.0096), whereas C-Myc overexpression did not correlate with the course of disease.
Mutation of Thr58 in lymphoma thus escapes this regulation resulting in accumulation of c-Myc protein, likely as part of the tumor progression.(Blood.2000;95:2104-2110)
In particular, amplification and overexpression of c-MYC in human breast cancers is associated with poor prognosis, although the genetic mechanisms by which c-MYC promotes tumor progression are poorly understood.
Iron plays a role in malignant cell growth, local invasion, and tumor progression, possibly due to changes in the expression of the proto-oncogene, c-myc.
While dysregulated beta-catenin may cause a transcriptional upregulation of the c-myc gene, the c-Myc protein expression appears to be further regulated by a posttranscriptional mechanism(s) during the process of neoplastic progression.
This study characterizes the frequency of exon 3 CTNNB1 mutations and compares the expression of CTNNB1 transcript variants and downstream targets MYC and WAF1 (p21) across the neoplastic progression of esophageal squamous cell carcinomas (ESCCs).
The MYC family oncogenes cause transformation and tumor progression by corrupting multiple cellular pathways, altering cell cycle progression, apoptosis, and genomic instability.
Conversely, forced expression of c-MYC enabled normal cells to accumulate NOXA and subsequently activate cell death programs in response to proteasome blockage. c-MYC is itself a proteasomal target whose levels or function are invariably up-regulated during tumor progression.
These results are surprising because current models suggest that Mad proteins should antagonize Myc proteins by competition for direct DNA binding via Max heterodimerization to inhibit cellular proliferation and potentially tumor progression.