Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer
A partir de l'analyse d'échantillons tumoraux prélevés sur 1 019 patients atteints d'un cancer colorectal, cette étude identifie les caractéristiques clinicopathologiques et moléculaires des tumeurs avec fusions du gène RSPO
Background : RSPO fusions that lead to WNT pathway activation are potential therapeutic targets in colorectal cancer (CRC), but their clinicopathological significance remains unclear.
Methods : We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription–PCR. The RSPO fusion-positive tumours were subjected to whole-exome sequencing (WES).
Results : 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.
Conclusion : RSPO fusion-positive CRCs constitute a rare subgroup of CRCs with several characteristic clinicopathological and genetic features.
British Journal of Cancer , article en libre accès, 2022