General information
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 with various tumour types, Coffin-Siris syndrome (OMIM #614607) and non-syndromic intellectual disability (OMIM #614562).
ARID1A (AT-rich interactive domain 1A) and ARID1B (AT-rich interactive domain 1B) proteins share 80% amino acid homology and are evolutionarily conserved. These proteins are integral components of the SWI/SNF chromatin modelling complex, which mediates epigenetic regulation in critical cellular processes such as cell differentiation, proliferation and DNA repair (Madan V et al. 2023).
Alterations in
ARID1A and
ARID1B genes are typically loss-of-function changes and they can exhibit bi-allelic inactivation or loss of protein expression, consistent with a tumour suppressor mechanism (Garraway and Lander, 2013).
ARID1A is frequently mutated across a wide variety of human cancers, whereas alterations in
ARID1B have been detected at lower frequencies.
ARID1A and
ARID1B genetic alterations have been identified in 11% of childhood neuroblastoma and are associated with early treatment failure and decreased survival (Sausen et al. 2012). Furthermore,
ARID1A inactivating mutations have been detected in approximately 50% of ovarian clear cell carcinomas (Jones et al. 2010, Wiegand et al. 2010, Caumanns JJ et al. 2018), in up to 17% of hepatocellular carcinomas (Guichard et al. 2012, Fujimoto et al. 2012, Huang et al. 2012), in 10-29% of gastric cancer cases (Wang et al. 2011, Zang et al. 2012) and in 37% of breast cancers (Cornen et al. 2012). Importantly, it has been shown that ARID1A-deficiency sensitizes cancer cells to PARP inhibitor therapies, providing new treatment possibilities for ARID1A-mutant tumours (Shen et al. 2015; Park et al. 2019; Yu et al. 2023).
Genetic alterations in
ARID1A (<5%) and
ARID1B (~37%) have also been detected in Coffin-Siris syndrome and non-syndromic intellectual disability cases.
ARID1A microduplications cause intellectual disability with recognizable syndromic features (Bidart et al. 2017), whereas intragenic duplications and microdeletions of
ARID1B have been described in patients with severe intellectual disability (Hoyer et al. 2012).
ARID1B alterations have also been found in patients with Coffin-Siris syndrome (Santen et al. 2012, Tsurusaki et al. 2012) and in patients affected with either syndromic or non-syndromic short stature (Yu et al. 2015).
This product is not CE/FDA registered for use in diagnostic procedures. The SALSA® MLPA® technique is covered by US patent 6,955,901 and corresponding patents outside the US. The purchase of this product includes a license to use only this amount of product solely for the purchaser’s own use.
Probemix content
P433-A2 ARID2A-ARID2B contains 56 MLPA probes with amplification products between 127 and 504 nucleotides (nt). This includes 22 probes for the
ARID2A and 22 probes for
ARID1B gene. In addition, 12 reference probes are included that detect autosomal chromosomal locations that target relatively stable copy number 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.