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Clinical Studies

Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer



RSPO fusions that lead to WNT pathway activation are potential therapeutic targets in colorectal cancer (CRC), but their clinicopathological significance remains unclear.


We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription–PCR. The RSPO fusion-positive tumours were subjected to whole-exome sequencing (WES).


Our analysis identified 29 CRCs with RSPO fusions (2.8%), consisting of five with an EIF3E-RSPO2 fusion and 24 with PTPRK-RSPO3 fusions. The patients were 17 women and 12 men. Thirteen tumours (45%) were right-sided. Histologically, approximately half of the tumours (13/29, 45%) had a focal or extensive mucinous component that was significantly more frequent than the RSPO fusion-negative tumours (13%; P = 8.1 × 10−7). Four tumours (14%) were mismatch repair-deficient. WES identified KRAS, BRAF, and NRAS mutations in a total of 27 tumours (93%). In contrast, pathogenic mutations in major WNT pathway genes, such as APC, CTNNB1 and RNF43, were absent. RSPO fusion status did not have a statistically significant influence on the overall or recurrence-free survival. These clinicopathological and genetic features were also confirmed in a pooled analysis of previous studies.


RSPO fusion-positive CRCs constitute a rare subgroup of CRCs with several characteristic clinicopathological and genetic features.

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Fig. 1: Histology of RSPO fusion-positive colorectal cancer.
Fig. 2: Summary of whole-exome sequencing analysis.
Fig. 3: Kaplan–Meier curves, stratified by RSPO fusion status.

Data availability

Nucleotide sequence data reported are available in the DDBJ database under the accession number JGAS000538.


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We thank Ms. Reiko Ogawa, Ms. Sachiko Miura, Ms. Toshiko Sakaguchi and Ms. Chizu Kina for their skilful technical assistance. We also thank Dr. Andrew Blake for help in data preparation. Part of the data used in the preparation of this manuscript were obtained and analysed from the datasets available through the MRC and CRUK funded S:CORT consortium.


This study was supported by Kurozumi Medical Foundation and JSPS KAKENHI Grant number 20K07382.

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Authors and Affiliations



TH, DT, KS and SS carried out experiments and analysed data. TH, JY, TN, YY and SS performed histological analyses. KN conducted the statistical analysis. TH and SS wrote the manuscript. DS, SK, SL, TM and AT provided clinicopathological and mutation data. RH reviewed the paper. All authors provided critical revisions of the final manuscript. All authors read and approved the final manuscript.

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Correspondence to Shigeki Sekine.

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The authors declare no competing interests.

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This study was approved by the Ethics Committee of the National Cancer Center Tokyo, Japan. The study was performed in accordance with the Declaration of Helsinki.

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Hashimoto, T., Takayanagi, D., Yonemaru, J. et al. Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer. Br J Cancer (2022).

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