General information
The SALSA MLPA Probemix P258 SMARCB1 is a research use only (RUO) assay for the detection of deletions or duplications in the SMARCB1 gene, inactivation of which has been associated with malignant rhabdoid tumours (MRTs). Rhabdoid tumours are a highly malignant group of neoplasms that usually occur in children under two years of age. MRTs of the kidney were first identified as a sarcomatous variant of Wilms tumours (Beckwith and Palmer, 1978). Later, extrarenal rhabdoid tumours were reported in numerous locations, including the central nervous system (CNS) (Parham et al., 1994). Classification has been difficult because of considerable variation in the histologic and immunologic characteristics within and between rhabdoid tumours of the liver, soft tissues, and CNS. In the CNS, rhabdoid tumours may be pure rhabdoid tumours or a variant that has been designated atypical teratoid/rhabdoid tumour (AT/RT) (Zin et al., 2021).

Germline alterations in SMARCB1 have also been associated with several genetic syndromes, including Coffin- Siris Syndrome 3 and SMARCB1-related schwannomatosis (Plotkin et al., 2022). Coffin-Siris Syndrome 3 (CSS3) is a congenital malformation syndrome characterized by developmental delay and intellectual disability, among other variable features. Patients with SMARCB1 alterations may have more severe neurodevelopmental deficits and structural brain abnormalities (Kosho et al., 2014). SMARCB1-related schwannomatosis (SWN) is characterized by the onset of multiple intracranial, spinal, or peripheral schwannomas. Affected individuals may also present multiple meningiomas. Individual schwannoma tumours from patients with schwannomatosis have been found to harbour somatic mutations in SMARCB1 (Sestini et al., 2008).

The protein encoded by the SMARCB1 gene (also known as INI1 or SNF5) is a core component of the SWI/SNF complex which is actively involved in remodelling chromatin structures, allowing the transcriptional machinery to access its targets more effectively. This ATP-dependent chromatin-remodelling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumour formation (Kalimuthu et al., 2016).

More information is available at http://www.ncbi.nlm.nih.gov/books/NBK469816/.

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 P258-C2 SMARCB1 contains 42 MLPA probes with amplification products between 127 and 445 nucleotides (nt). This includes two probes for each exon of the SMARCB1 gene (nine exons). In addition, this probemix includes 10 probes flanking SMARCB1 in 22q11 and 22q12 chromosomal regions, and 14 reference probes that detect several autosomal chromosomal locations. Complete probe sequences and the identity of the genes detected by the reference probes are available in Table 2b of the Product Description and 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.