Search results for "chromosome instability"

Patterns of genomic instability in gastric cancer: clinical implications and perspectives

2007

In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to th…

Post-transplant consolidation based on combination of lenalidomide and proteasome inhibitors in multiple myeloma

2021

Multiple myeloma (MM) is a hematological malignancy due to uncontrolled proliferation of neoplastic plasma cells in the bone marrow, associated to chromosomal instability and cytogenetic abnormalities, which could have an impact on prognosis. Response to treatment and survival of newly diagnosed myeloma patients is heterogeneous, with median overall survival ranging from two to more than ten years, due to clinical and biological factors. To warrant long-term control of disease, several strategies have been proposed in the last years, including short-term high-dose of treatment, named as consolidation, before maintenance. This review will discuss the role of consolidation in the current myel…

Microsatellite Instability in Colorectal Cancer: Time to Stop Hiding!

2011

Colorectal cancer (CRC) is the second cause of cancer-related death worldwide. Surgery constitutes the primary therapy for these tumors, together with chemotherapy that is usually recommended in patients with metastatic primary CRC. Although molecularly distinct entities arising from different physiopathogenic mechanisms - microsatellite (MSI) and chromosomal instability (also called microsatellite stable, MSS) - have been characterized in CRC, there is still no specific therapeutic approach that takes into account disease’s molecular heterogeneity [1]. MSI is observed in 1015% of sporadic CRCs. MSI CRCs displayed particular morphologic features, with greater predilection for the right colo…

Identification of molecular markers involved in cellular response to aneuploidy in normal and tumor cells

2020

DNA DEMETHYLATION CAUSED BY 5-AZA-2’-DEOXYCYTIDINE TREATMENT AFFECTS GENOME STABILITY BY INDUCING MITOTIC ALTERATIONS AND ANEUPLOIDY IN HCT-116 TUMOR…

2014

RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation

2009

BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…

snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis

2013

AbstractAmplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance,most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to …

Does the evidence matter in medicine? The retinoblastoma paradigm.

2007

Retinoblastoma (Rb) is the most common intraocular malignant tumour in childhood, with an incidence of 1 in 15,000 live births. Complete information on this rare tumour can be easily accessed through the internet, although many aspect concerning the aetiology and pathogenesis of the disease, are still controversial. The "two hit" theory, formulated in 1971 to explain the variegated clinical expression of the disease, is based on the idea that single gene mutation may determine the development of cancer. However, this view does not take into account the most recent evidences showing the role of aneuploidy and chromosome instability in cancer. Also, a number of other genes and epigenetic mech…