You won't believe this old test … that does cheap single-cell mutation detection

Abstract

Detecting mutations in single cells from cancer specimens is now a major area of translational research. In a recent article in this journal, Khalique et al validated an immunohistochemistry assay for ARID1A that reliably identifies loss of function mutations in single cells in tissue sections. This work exemplifies best practice for developing and orthogonally validating immunohistochemical assays to provide clearly interpretable mutational results with spatial context.

Keywords: Female reproductive system; Immunohistochemistry; Mutation; Ovary; Testing.

Figure 1

(A) H&E photomicrograph of endometrial endometrioid carcinoma, grade 3; (B) absence of MSH6 suggesting mismatch repair deficiency (additional MSH2 absence not shown). The arrow shows positive internal control stromal staining; (C) small focus of subclonal ARID1A loss (asterisk); (D) focus of p53 overexpression overlying but extending beyond the ARID1A focus (asterisk). Taken together these panels suggest a prototypical somatic mismatch repair deficiency resulting in subclonal TP53 missense alteration, and subsequent ARID1A loss of function mutation.