General information: The SALSA MLPA Probemix P417 BAP1 is a research use only (RUO) assay for the detection of deletions or duplications in the BAP1 gene, which is associated with BAP1 tumour predisposition syndrome.

The BAP1 (BRCA1 associated protein 1) gene is a tumour suppressor gene that functions in the BRCA1 growth control pathway and has an important role controlling in cell proliferation and growth inhibition. The BAP1 gene locates in the 3p21 region, which is frequently affected by LOH or deletions in several cancer types including lung, breast and ovarian cancer, but also in uveal melanoma and mesothelioma.

BAP1 tumour predisposition syndrome (OMIM# 614327) is inherited in an autosomal dominant manner. Individuals carrying heterozygous BAP1 mutations are at high-risk for the development of a variety of tumours, including benign melanocytic tumours as well as several malignant tumours, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, and other cancer types, such as renal cell carcinoma, basal cell carcinoma, lung adenocarcinoma and meningioma (Wiesner et al. 2011, Abdel-Rahman et al. 2011, Boru et al. 2019).

In addition, research suggests that uveal melanoma with monosomy of chromosome 3 (frequency 50-60% of all uveal melanomas) represents a distinct pathological entity as compared to uveal melanoma with normal disomy 3. The putative target gene on the 3p arm is BAP1, as inactivating somatic mutations of BAP1 are identified in >80% of patients with metastasizing uveal melanoma (Harbour et al. 2010). Moreover, BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma (Testa et al. 2011, Bott et al. 2011).

More information about BAP1 tumour predisposition syndrome is available at:
https://www.ncbi.nlm.nih.gov/books/NBK390611/

Probemix content: The SALSA MLPA Probemix P417-B3 BAP1 contains 42 MLPA probes with amplification products between 132 and 395 nucleotides (nt). This includes 17 probes for the BAP1 gene and 10 flanking probes included for the determination of the extent of the deletion or duplication. In addition, 14 reference probes are included that detect target relatively copy number stable regions in various cancer types including melanocytic tumours and mesothelioma. The identity of the genes detected by the reference probes are available in Table 2b in the product description and online (www.mlpa.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.mlpa.com.