Molecular inversion probes: a novel microarray technology and its application in cancer research

The molecular inversion probe (MIP) assay technology was originally developed for single nucleotide polymorphism (SNP) genotyping, but has subsequently been used for identifying other types of genetic variation including focal insertions and deletions, larger copy number alterations (CNAs), loss of heterozygosity (LOH), and most recently, for somatic mutation detection. The assay requires as little as 75 ng of genomic DNA and has been shown to perform well with highly degraded DNA, such as that from formalin-fixed paraffin-embedded (FFPE)-preserved samples from 20 years ago or older. Central to the MIP assay technology are the padlock probes that hybridize to the DNA target of interest before polymerase chain reaction amplification, leading to high assay specificity. As outlined in this review, the MIP assay has enabled new discoveries and a deeper understanding of the molecular basis of cancer and its various disease subtypes. The use of novel genomic technology such as MIPs on clinically archived FFPE samples has the potential to lead to more accurate disease diagnosis, prognosis, and novel therapeutic intervention. This review describes the initial history of MIP technology, details of the MIP assay, its current analysis techniques, and recent publications related to this novel platform.