The SALSA MLPA Probemix P260 PALB2-RAD50-RAD51C-RAD51D is an in vitro diagnostic (IVD)1
or research use only (RUO) semi-quantitative assay2
for the detection of deletions or duplication in the human PALB2
in genomic DNA isolated from human peripheral whole blood specimens. P260 PALB2-RAD50-RAD51C-RAD51D is intended to confirm a potential cause for breast, ovarian and other cancer types in patients who are negative for BRCA1
mutations. This product can also be used to determine increased cancer susceptibility in at-risk family members. Moreover, copy number variations in PALB2
can also confirm a potential cause for and clinical diagnosis of autosomal recessive Fanconi Anemia type N.
Copy number variations (CNVs) detected with P260 PALB2-RAD50-RAD51C-RAD51D should be confirmed with a different technique. In particular, CNVs detected by only a single probe always require confirmation by another method. Most defects in the PALB2
genes are point mutations, none of which will be detected by MLPA. It is therefore recommended to use this assay in combination with sequence analysis.
Please note that this probemix covers all exons of PALB2
, but not of RAD50
Assay results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods, clinical genetic evaluation, and counselling, as appropriate. The results of this test should be interpreted by a clinical molecular geneticist or equivalent.
This device is not intended to be used for standalone diagnostic purposes, pre-implantation or prenatal testing, population screening, or for the detection of, or screening for, acquired or somatic genetic aberrations, e.g. from DNA extracted from formalin-fixed paraffin embedded (FFPE) or fresh tumour materials.
Please note that this probemix is for in vitro diagnostic (IVD) use in the countries specified at the end of this product description. In all other countries, the product is for research use only (RUO).
To be used in combination with a SALSA MLPA Reagent Kit and Coffalyser.Net analysis software.
all play a role in DNA damage repair and a defect in one of these genes can lead to increased risk of tumour formation. For breast cancer, autosomal dominant mutations in the genes BRCA1
are the most frequent cause, followed by mutations in PALB2
, though with a much lower frequency (Buys et al. 2017). Mutations in PALB2
may also increase the risk of developing pancreatic cancer, although the evidence is limited (see Table A). Defects in both PALB2
copies can result in Fanconi Anemia (FA) type N. FA is characterized by physical abnormalities (such as short stature or abnormal skin pigmentation), bone marrow failure, and increased risk for malignancies. The incidence of FA in general is 1:160,000 - of which type N comprises less than one percent of the cases. FA type N is associated with an unusually severe predisposition to paediatric malignancies (https://www.ncbi.nlm.nih.gov/books/NBK1401/
Autosomal dominant mutations in RAD51C
result in increased risk for cancer, in particular ovarian cancer, while evidence of an association between RAD50
mutations and cancer risk is currently limited (see Table A).
The SALSA MLPA Probemix P260-C1 PALB2-RAD50-RAD51C-RAD51D contains 50 MLPA probes with amplification products between 130 and 500 nucleotides (nt). This includes 13 probes for the PALB2
gene, nine probes for the RAD51C
gene, ten probes for the RAD51D
gene, and eight probes for the RAD50
gene. At least one MLPA probe is present for each exon of PALB2, RAD51C
. For RAD50
, the eight probes are distributed evenly over the gene, including the first and last exon. In addition, ten reference probes are included that detect autosomal chromosomal locations. 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