General information
The SALSA MLPA Probemix P433 ARID1A-ARID1B is a research use only (RUO) assay for the detection of deletions or duplications in the ARID1A and ARID1B genes, which are associated various with various tumour types, Coffin-Siris syndrome and mental retardation syndrome.
The ARID1 subfamily contains two members: ARID1A (AT-rich interactive domain 1A) and ARID1B (AT-rich interactive domain 1B), which share 80% amino acid homology and are evolutionarily conserved. These genes encode proteins for the SWI/SNF chromatin modelling complex. Both ARID1A and ARID1B are able to bind DNA and are suggested to help target the SWI/SNF complexes to the chromatin location that needs to be remodelled.
Chromosomal deletions and mutations of ARID1A and ARID1B have been identified in 11% of childhood neuroblastoma and are suggested to associate with early treatment failure and decreased survival. Approximately 50% of ovarian clear cell carcinomas carry inactivating mutations in ARID1A (Jones et al. 2010, Wiegand et al. 2010). ARID1A is located at 1p36.11 chromosomal band, which is suggested to contain several tumour-suppressor genes and, which is also commonly deleted in different tumour types. Frequent ARID1A aberrations have been observed in many cancer types, including up to 17% of hepatocellular carcinomas (Guichard et al. 2012, Fujimoto et al. 2012, Huang et al. 2012), 10-29% of gastric cancers (Wang et al. 2011, Zang et al. 2012) and up to 37% of breast cancers (Cornen et al. 2012). Loss of ARID1A expression is associated with poor prognosis in urothelial bladder cancer (Balbás-Martínez et al. 2013). Intragenic deletions of ARID1B have been detected in 90% of neuroblastoma patient samples (Sausen et al. 2012). ARID1A and ARID1B aberrations are typically loss-of-function changes; they can exhibit bi-allelic inactivation or loss of protein expression, consistent with a tumour suppressor mechanism (Garraway and Lander, 2013).
Moreover, ARID1A and ARID1B genes have been implicated in Coffin-Siris syndrome and in mental retardation (OMIM 614607 and OMIM 614562). Both intragenic duplications and microdeletions of ARID1B have been described in patients with unexplained intellectual disability (Hoyer et al. 2012), in patients with Coffin-Siris syndrome (Santen et al. 2012, Tsurusaki et al. 2012) and with both syndromic and non-syndromic short stature (Yu et al. 2015). Also, ARID1A microduplications causes intellectual disability with recognizable syndromic features (Bidart et al. 2017).

Probemix content
The SALSA MLPA Probemix P433-A2 ARID1A-ARID1B contains 56 MLPA probes with amplification products between 127 and 504 nucleotides (nt). This includes 22 probes for the ARID1A and 22 probes for ARID1B gene. In addition, 12 reference probes are included that detect autosomal chromosomal locations that target relatively copy number stable regions in various cancer types. Complete probe sequences are available online (www.mrcholland.com) and the identity of the genes detected by the reference probes is available in Table 3 of the product description.
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.