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

Authors

Shogen Boku, Takao Fujisawa, Tomofumi Sakagami, Shigenori Kadowaki, Hironaga Satake, Hisateru Yasui, Koushiro Ohtsubo, Yasushi Shimizu, Tomoyuki Otsuka, Bunya Kuze, Riu Yamashita, Taro Shibuki, Yoshiaki Nakamura, Hideaki Bando, Takayuki Yoshino, Milan Radovich, Masao Yagi, Susumu Okano

Published in

Frontiers in oncology. Volume 16. Pages 1967793. Epub Sep 24, 2026.

Abstract

Secretory carcinoma of the salivary gland is a rare, fusion-driven malignancy in which kinase fusions can serve as therapeutic targets. 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. Research WTS did not constitute an approved companion diagnostic result, and the approved DNA report did not establish an actionable ETV6::RET finding; selpercatinib was therefore not initiated. When DNA profiling yields unresolved rearrangement signals, a clinically validated RNA-based fusion assay and an appropriate regulatory framework for treatment selection may improve access to matched therapy.

PMID:
42851375
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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