General information
The SALSA MLPA
Probemix P323 CDK4-HMGA2-MDM2 is a
research use only (RUO) assay for the detection of deletions, gains or amplifications of
CDK4, HGMA2, MDM2 and other genes on chromosome 12.
Alterations of the
CDK4,
MDM2 and
HMGA2 genes are suggested to be of diagnostic, clinical and/or prognostic relevance in liposarcoma, osteosarcoma, rhabdomyosarcoma, adenomas and carcinomas of the salivary gland, and in pituitary adenomas. In well-differentiated (WDLPS) and dedifferentiated (DDLPS) types of liposarcomas, the
MDM2 and
HMGA2 genes are recurrently amplified, which can differentiate them from benign lipomas (Italiano et al. 2008). DDLPS and WDLPS patients with only
HMGA2-
MDM2 amplification are suggested to have a favourable prognosis compared to patients with both
HMGA2-
MDM2 and
CDK4 amplifications (Italiano et al. 2009). In osteosarcoma (OS),
MDM2-
CDK4 amplification can be used in differential diagnostics, as it seems to be most prevalent in parosteal OS (Mejia-Guerrero et al. 2010). Amplifications of the 12q13-q14 region (including the
GLI1,
TSPAN31,
CDK4,
HMGA2 and
MDM2 genes) are common in leiomyosarcoma and alveolar, embryonal and sclerosing rhabdomyosarcoma, and correlate with poor survival in alveolar rhabdomyosarcoma (Barr et al. 2009).
HMGA2 amplifications are characteristic for pituitary adenomas, and especially for prolactiomas (Finelli et al. 2002) and also observed in adenomas and carcinomas of salivary glands (Persson et al. 2009).
In addition, the P323 CDK4-HMGA2-MDM2 probemix can be used for the analysis of other tumor types to detect copy number alterations affecting genes on chromosome 12, that are targeted by this P323 probemix. These include 12q chromosomal arm copy number alterations resulting in
CDK4 and
MDM2 amplification in glioma’s (Reifenberger et al. 1993; Reifenberger et al., 1996; Rollbrocker at al. 1996; Hoadly et al 2018),
CCND2 amplifications in colon adenocarcinoma, ovarian serous adenocarcinoma and testicular germ cell tumors (AACR Project GENIE Consortium, 2017; Hoadly et al. 2018), copy number loss within the 12p chromosomal arm in multiple myeloma (Munshi et al. 2011; Hung et al. 2021) and acute lymphoblastic leukemia (ALL) (Raynaud et al. 1996; Wiemels et al. 2008), and trisomy 12 observed in chronic lymphocytic leukemia (CLL) (Döhner et al. 2000; Haferlach et al. 2007; Autore et al. 2018).
This SALSA MLPA probemix is not CE/FDA registered for use in diagnostic procedures. Purchase of this product includes a limited license for research purposes.
Probemix content
The SALSA MLPA Probemix P323-B2 CDK4-HMGA2-MDM2 contains 50 MLPA probes with amplification products between 124 and 478 nucleotides (nt). This includes 36 probes for detecting copy number changes in chromosome 12, including two probes for the CDK4 gene at 12q14.1, five probes for the HMGA2 gene at 12q14.3 (one for each exon) and four probes for the MDM2 gene at 12q15. In addition, 14 reference probes are included which target relatively copy number stable regions in various cancer types. Complete probe sequences and the identity of the genes detected by the reference probes are available online (
www.mrcholland.com). This probemix contains nine quality control fragments generating amplification products between 64 and 105 nt: four DNA Quantity fragments (Q-fragments), two DNA Denaturation fragments (D-fragments), one Benchmark fragment, and one chromosome X and one chromosome Y-specific fragment. More information on how to interpret observations on these control fragments can be found in the MLPA General Protocol and online at
www.mrcholland.com.