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Cutaneous melanoma, familial; Pancreatic cancer syndromes

Region: CDKN2A 9p21.3; CDKN2B 9p21.3; CDK4 12q14.1; MITF E318K 3p14.1

General information
The SALSA MLPA Probemix P419 CDKN2A/2B-CDK4 is a research use only (RUO) assay for the detection of deletions or duplications in the CDKN2A, CDKN2B and CDK4 genes, which are associated with familial cutaneous melanoma, neural system tumour- and pancreatic cancer syndromes. This probemix can also be used to detect the presence of a MITF p.E318K (c.952G>A) point mutation and the status of codon 24 of the CDK4 gene with a WT probe.

Malignant melanoma is estimated to be hereditary in 5-10% of the cases. Familial cutaneous melanoma arises in an autosomal-dominant pattern within the affected families, and germline alterations in the CDKN2A gene (9p21.3) are detected in up to 40% of cases (Goldstein et al. 2007). The CDKN2A gene encodes for two proteins read in alternative reading frames, namely p16INK4A and p14ARF. The majority of CDKN2A mutations detected in familial melanoma patients affect exons 1 and 2, which code for p16INK4A. However, exon 1 mutations specific for p14ARF have also been reported (Hewitt et al. 2002), as well as larger genomic deletions of CDKN2A (Randerson-Moor et al. 2001; Knappskog et al. 2006; Lesueur et al. 2008). Moreover, both heterozygous and homozygous deletions harbouring both CDKN2A and CDKN2B are frequently detected in somatic melanoma samples (Flores et al. 1996).

Another high-penetrance, but low-frequency, melanoma susceptibility gene is CDK4 (12q14.1), which is mutated in 2% of the melanoma families (Goldstein et al. 2007). Two point mutations (p.R24H and p.R24K) of CDK4 have been detected in familial melanoma cases (Zuo et al. 1996). In addition, a germline mutation p.E318K (c.952G>A) in the MITF gene has been suggested to associate with predisposition to familial melanoma (Yokoyama et al. 2011; Bertolotto et al. 2011).

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 P419-B1 CDKN2A/2B-CDK4 contains 57 MLPA probes with amplification products between 121 and 504 nucleotides (nt). This includes 14 probes for the CDKN2A gene, nine probes for the CDKN2B gene, nine probes for the CDK4 gene and 10 flanking probes in total for the CDKN2A and CDKN2B genes. Furthermore, this probemix contains one probe specific for the MITF p.E318K (c.952G>A) point mutation, which will only generate a signal when the mutation is present, and one wildtype probe for CDK4 codon 24, which will have a drop in signal in case of a CDK4 codon 24 mutation. In addition, 13 reference probes are included that detect relatively copy number stable regions in various cancer types, including cutaneous melanoma. Complete probe sequences and the identity of the genes detected by the reference probes are available in Table 3 and online (

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, 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

SALSA Binning DNA SD008
The SD008 Binning DNA provided with this probemix can be used for binning of all probes including the MITF mutation-specific probe (probe 17808-L23191 at 162 nt). SD008 Binning DNA is a mixture of genomic DNA from healthy individuals and plasmid DNA that contains the target sequence detected by the above mentioned probe. Inclusion of one reaction with 5 μl SD008 Binning DNA in initial MLPA experiments is essential as it can be used to aid in data binning of the peak pattern using Coffalyser.Net software. Furthermore, Binning DNA should be included in the experiment whenever changes have been applied to the set-up of the capillary electrophoresis device (e.g. when capillaries have been renewed). Binning DNA should never be used as a reference sample in the MLPA data analysis, neither should it be used for quantification of mutation signals. It is strongly advised that all samples tested are extracted with the same method and derived from the same source of tissue. For further details, please consult the SD008 Binning DNA product description, available online: This product is for research use only (RUO).

Sample DNA
Sample DNA developed for this product:

Order Items


Item no.
SALSA MLPA Probemix P419 CDKN2A/2B-CDK4 – 25 rxn
€ 260.00
SALSA MLPA Probemix P419 CDKN2A/2B-CDK4 – 50 rxn
€ 510.00
SALSA MLPA Probemix P419 CDKN2A/2B-CDK4 – 100 rxn
€ 998.00

Required Reagents (Sold Separately)

Item no.
SALSA MLPA Reagent Kit – 100 rxn – FAM
€ 316.00
SALSA MLPA Reagent Kit – 100 rxn – Cy5
€ 316.00
SALSA MLPA Reagent Kit – 500 rxn – FAM
€ 1455.00
SALSA MLPA Reagent Kit – 500 rxn – Cy5
€ 1455.00
SALSA MLPA Reagent Kit – 2000 rxn – FAM
€ 5590.00

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SALSA MLPA Probemix ME024 9p21 CDKN2A/2B region

Contains probes for detection of methylation and/or copy number status of the chromosomal region 9p21.3 (CDKN2A/2B, CDKN2B-AS1, MTAP, MIR31, and PAX5).


Contains four probes for the detection of methylation status of the CDKN2A gene.

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