Probes for KRAS

Abstract

AIMS:

Traditional serrated adenoma (TSA) is an uncommon type of colorectal serrated polyp. RSPO fusions, which potentiate WNT signaling, are common and characteristic genetic alterations in TSA. The aim of this study was to further characterize the prevalence and variation of RSPO fusions in TSA.

METHODS AND RESULTS:

Quantitative PCR analysis of 99 TSAs revealed overexpression of RSPO2 and RSPO3 in 6 and 29 lesions, respectively. Reverse-transcription PCR identified previously reported PTPRK-RSPO3 fusion transcripts in all the 29 TSAs with RSPO3 overexpression, confirming that PTPRK-RSPO3 is the predominant RSPO fusions in TSAs. Among the six lesions with RSPO2 overexpression, two overexpressed full-length RSPO2. An EIF3E-RSPO2 fusion, which is a known recurrent RSPO fusion in colorectal cancer, was detected in three lesions. In addition, rapid amplification of cDNA ends identified a novel PIEZO1-RSPO2 fusion in one TSA. All the four TSAs with RSPO2 fusions concurrently had KRAS mutations and showed the classical histological features.

CONCLUSIONS:

The present study identified EIF3E-RSPO2 and PIEZO1-RSPO2 fusions in TSAs. Our observations expand the spectrum of RSPO fusions in TSAs and suggest that TSAs are precursors of colorectal cancers with these RSPO2 fusions.