Hashimoto, Taiki, Takayanagi, Daisuke, Yonemaru, Junpei, Naka, Tomoaki, Nagashima, Kengo, Yatabe, Yasushi, Shida, Dai, Hamamoto, Ryuji, Kleeman, Sam O, Leedham, Simon J, Maughan, Timothy, Takashima, Atsuo, Shiraishi, Kouya, Sekine, Shigeki (October 2022) Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer. British Journal of Cancer, 127 (6). pp. 1043-1050. ISSN 0007-0920
Abstract
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.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > neoplasms diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types > colon cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Janowitz lab School of Biological Sciences > Publications |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | October 2022 |
| Date Deposited: | 24 Jun 2022 15:26 |
| Last Modified: | 29 Feb 2024 17:09 |
| PMCID: | PMC9470590 |
| URI: | https://repository.cshl.edu/id/eprint/40662 |
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