[1] An application of this technique for early detection of lung cancer (Lung-CLiP) was originally described by Chabon et al. (2020)[2] from the labs of Ash Alizadeh and Max Diehn at Stanford.
[3][4] This method relies on several improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)[5] for analysis of circulating tumor DNA (ctDNA).
For example, studies have shown that the majority of somatic mutations found in cell-free DNA (cfDNA) are not tumor derived, but instead reflect clonal hematopoeisis (also known as CHIP).
[2][6] Even though CHIP tends to target specific genes, it also involves many generally non-recurrent mutations that can be shed from leukocytes and detected in cfDNA, regardless of whether profiling patients with cancer and healthy adults.
[2] While the CLiP method is unique in relying exclusively on mutations and copy number alterations, it is related to a variety of other liquid biopsy methods being commercially developed for early cancer detection using ctDNA and proteins (e.g., CancerSEEK / DETECT-A [7]), cfDNA fragmentation patterns (e.g., DELFI),[8][9] and DNA methylation (e.g., cfMeDIP-Seq,[10] Grail[11]).