RSPO3

Overview

RSPO3 (R-Spondin 3) is a secreted Wnt pathway activator. Recurrent PTPRK-RSPO3 gene fusions were identified in colorectal cancer as the most frequent RSPO alteration (~8% of CRC), providing an alternative Wnt pathway activation mechanism. These fusions define a novel molecular subset of CRC distinct from APC-mutant tumors.

Alterations observed in the corpus

• PTPRK(e1)-RSPO3(e2) and PTPRK(e7)-RSPO3(e2) fusions found in 8% of colorectal tumors; activates Wnt signalling; mutually exclusive with APC mutations PMID:22895193

Cancer types (linked)

• COAD: PTPRK-RSPO3 fusions in 8% (WES, Genentech CRC cohort, 74 tumors); the most frequent RSPO alteration in this cohort PMID:22895193

Co-occurrence and mutual exclusivity

• Mutually exclusive with APC mutations and CTNNB1 mutations; co-occurs with KRAS mutations in some samples PMID:22895193

Therapeutic relevance

• RSPO fusion-positive tumors represent attractive targets for antibody-based therapy directed against R-spondin proteins PMID:22895193

Open questions

Sources

• PMID:22895193

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