POLE Mutation
Order Code: POLE
CPT Code: 81479, 88381
Effective October 6, 2021 MLabs will offer POLE Mutation testing.
Test Usage: DNA polymerase epsilon, encoded by the POLE gene, is involved in DNA replication and repair. Somatic POLE mutations, primarily affecting the exonuclease domain and proofreading capability of this polymerase, are present in approximate 5-16% of endometrial carcinomas and define a subgroup with numerous mutations (‘ultramutated’; ≥ 100 mutations/Mb), enhanced immune response and excellent clinical outcomes. Somatic POLE mutations are also present in 1-2% of colorectal carcinomas. Endometrial carcinomas with pathogenic POLE mutations have thus been codified as a distinct clinical entity according to the National Comprehensive Cancer Network (NCCN) guidelines . The most common POLE mutations include P286R, V411L, S297F, A456P and S459F. However, a wide variety of other, less common POLE variants have been described including some that are not associated with the ‘ultramutated’ genomic signature or whose potential pathogenicity is not known. Germline POLE mutations – particularly L242V – are also described and are associated with polymerase proofreading-associated polyposis syndrome (PPAP). If there is a clinical suspicion of germline POLE mutation, POLE sequencing of peripheral blood is recommended.
This DNA based test is performed by Sanger Sequencing of POLE exons 9, 11, 13 and 14 (NM_006231). The limit of detection of this assay is 50% mutation-bearing cells.
Collection Instructions: For formalin-fixed, paraffin-embedded tissue, a block containing an area with a high percentage of neoplastic cells (for micro-/macro-dissection) is preferred. Unstained, UNBAKED slides (5-8, 10-micron slides; 10-15 if few neoplastic cells are present) with associated H&E-stained slide are also acceptable. Decalcified tissue or other fixatives will be accepted and the assay attempted; however, these may result in failed testing due to degraded nucleic acid. Both blocks and slides should be stored at room temperature. A Diff-Quik or Papanicolaou stained aspirate smear (preferably containing a high percentage and overall number of neoplastic cells) is also acceptable. Store at room temperature.
Alternate Specimen
For exhausted formalin-fixed, paraffin-embedded blocks, the original Hematoxylin and Eosin-stained slide(s) may be extracted at the discretion of the extracting pathologist. The extraction process will result in destruction of these slide(s); however, a digital image of the slide(s) must be collected prior to extraction and retained for a minimum of 10 years from the specimen collection date.
Previously extracted DNA from a CLIA certified laboratory may be accepted; however, the extracting laboratory must take responsibility for ensuring that viable, neoplastic cells comprise at least 50% of cellularity within the extracted sample.
Analytic Time: 3-10 days