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, HMGA2, 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 prolactinomas (Finelli et al. 2002), and are 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 tumour 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 tumours (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).
