Table 1_Case Report: Discordance between RNA-identified ETV6::RET and clinically reportable DNA profiling in salivary gland secretory carcinoma.docx

We report a patient with an ETV6::RET-positive tumor who achieved a complete response to pralsetinib and subsequently developed resistance. Research whole-transcriptome sequencing (WTS) of the resistant lesion identified an expressed in-frame ETV6::RET transcript retaining the RET kinase domain, with 300 and 196 split reads at the two breakpoints and three discordant mate pairs; research whole-exome sequencing provided limited concordant DNA-level support.

A clinically approved targeted DNA-based comprehensive genomic profiling assay applied to material from the same lesion detected RET intron 11 and ETV6 intron 6 rearrangement signals but did not report actionable ETV6::RET or RET p.L730V. Under the Japanese regulatory framework applicable when selpercatinib was considered, an approved in vitro diagnostic or medical device was required to confirm a RET fusion for non-lung, non-thyroid solid tumors.