XL MDM2 consists of an orange-labeled probe hybridizing to the MDM2 gene region at 12q15 and a green-labeled probe hybridizing to the centromere of chromosome 12.

Probe maps are created in accordance with the intended purpose of the product. Solid colored bars do not necessarily indicate that the probe fully covers the indicated genomic region. Therefore, caution is advised when interpreting results generated through off-label use. Probe map details based on UCSC Genome Browser GRCh37/hg19. Map components not to scale. Further information is available on request.

The tumor suppressor gene TP53 is a key regulator in the cell cycle and is involved in apoptosis, genomic stability and angiogenesis. Inactivation of TP53 function prevents the antiproliferative effect and contributes to the development of many types of cancer. Several mechanisms of TP53 loss of function are known such as gene mutations, interaction of p53 with viral proteins and association of p53 with the MDM2 oncoprotein. MDM2 is an ubiquitin ligase negatively regulating p53. MDM2 is amplified in about 7% of all human cancers with the highest frequency of about 20% in soft tissue tumors. MDM2 might also have p53-independent transforming capabilities. Well-differentiated liposarcomas/atypical lipomatous tumors (WDL-ALT) and dedifferentiated liposarcomas are among the most common soft tissue tumors in adults. Both entities share the same genetic aberration, an amplification of the chromosomal region including MDM2. WDL-ALT and benign lipomatous tumors can be morphologically similar and a clear assignment based on histological features might be difficult. The analysis of the MDM2 amplification status by FISH is considered as a useful technique for the differential diagnosis of WDL-ALT and benign lipomatous tumors since benign lesions do not harbor MDM2 amplifications. Furthermore, MDM2 overexpression has been reported to be a potential cause of p53 dysfunction in chronic lymphoblastic leukemia.

Clinical Applications

• Chronic Lymphocytic Leukemia (CLL)

XL MDM2 hybridized to lymphocytes. Two normal interphases and one normal metaphase are shown.

• Haidar et al (1997) Am J Hematol 54:189-195
• Momand et al (1998) Nucleic Acids Res 26:3453-3459
• Weaver et al (2008) Mod Pathol 21:943-949

• Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.
• A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature.
• Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.
• Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.
• Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.
• Fluorescence in situ hybridisation assays designed for del(7q) detection uncover more complex rearrangements in myeloid leukaemia cell lines
• Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation.
• A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasiaresulting in a fusion of IGL and CCND1: case report.
• Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions.