General information
The SALSA MLPA
Probemix P474 CD274-PDCD1LG2-JAK2 is a
research use only (RUO) assay for the detection of deletions or duplications in the
CD274 (also known as
PDCD1LG1 or
PDL1),
PDCD1LG2 (also known as
PDL2) and
JAK2 genes located on 9p24.1.
Amplification of the
CD274 gene, often co-amplified with
PDCD1LG2 and
JAK2, has been described in various types of cancer. In nearly all cases of classical Hodgkin lymphoma the copy number of
CD274 and
PDCD1LG2 is increased, either by amplification, copy gain or polysomy, but only amplification of 9p24.1 correlates with shorter progression-free survival (Roemer et al. 2016). Likewise,
JAK2 copy number is increased in 64% of classical Hodgkin lymphoma cases (Van Roosbroeck et al. 2016).
In addition, in various subtypes of lung cancer, amplification of 9p24.1 is common; in 40-43% of pulmonary squamous-cell and adenocarcinomas, in 5-16% of non-small cell lung cancer (NSCLC) and in 2-5% of small cell lung cancer
CD274,
PDCD1LG2 and/or
JAK2 copy number is increased (Clavé et al. 2018; Goldmann et al. 2016; Ikeda et al. 2015; Inoue et al. 2016; George et al. 2016; Iwakawa et al. 2013). In non-squamous NSCLC CD274 copy number may predict different response to immune checkpoint inhibitor treatment (Murugesan et al. 2022).
In certain types of soft-tissue sarcoma
CD274 copy number gains are also common, for example in 34-60% of undifferentiated pleomorphic sarcomas and in 35% of myxofibrosarcomas (Boxberg et al. 2017; Budczies et al. 2017). But also in 29% of triple negative breast carcinomas, in 19% of oral squamous cell carcinomas, in 5% of glioblastomas, in 3% of anaplastic thyroid carcinomas, and in 1-3% of colon carcinomas an increased copy number of
CD274,
PDCD1LG2 and/or
JAK2 is found (Barrett et al. 2015; Straub et al. 2016; Pozdeyev et al. 2018; Lee et al. 2018).
Interestingly, in a large study on 22 major cancer types it became apparent that deletions of
CD274 are more frequent (31%) than amplifications (12%) and both types of copy number alterations are associated with dismal prognosis (Budczies et al. 2016).
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 P474-A1 CD274-PDCD1LG2-JAK2 contains 51 MLPA probes with amplification products between 124 and 500 nucleotides (nt). This includes seven probes for the
CD274 gene, 10 probes for the
PDCD1LG2 gene and 12 probes for the
JAK2 gene. In addition, 17 reference probes are included that target relatively copy number stable regions in various cancer types. Probe sequences and the identity of the genes detected by the reference probes are available in Table 3 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.