ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Prevalence of recurrent oncogenic fusion in mismatch repair-deficient colorectal carcinoma with hypermethylated MLH1 and wild-type BRAF and KRAS.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- The preventive and carcinogenic effect of metals on cancer: a systematic review.BMC public health · 2024Pooled it
- Systematic review of NTRK 1/2/3 fusion prevalence pan-cancer and across solid tumours.Scientific reports · 2023Pooled it
- Adjuvant FOLFIRINOX versus S-1 monotherapy for resected PDAC: retrospective real-world data.Therapeutic advances in medical oncology · 2026Article
- S-1 plus oxaliplatin versus modified FOLFIRINOX for advanced pancreatic adenocarcinoma after gemcitabine plus nab-paclitaxel failure.Therapeutic advances in medical oncology · 2025Article
- Mutation profile and molecular heterogeneity in mismatch repair deficient endometrial carcinoma.Frontiers in oncology · 2025Article
- High prevalence of NTRK fusions in sporadic dMMR/MSI mCRC RAS/RAF wild-type: an opportunity for a post-immune checkpoint inhibitors progression rescue strategy.ESMO gastrointestinal oncology · 2024Article
- SWI/SNF complex gene variations are associated with a higher tumor mutational burden and a better response to immune checkpoint inhibitor treatment: a pan-cancer analysis of next-generation sequencing data corresponding to 4591 cases.Cancer cell international · 2022Article
- Liquid biopsy using ascitic fluid and pleural effusion supernatants for genomic profiling in gastrointestinal and lung cancers.BMC cancer · 2022Article
- A lung adenocarcinoma patient with co-mutations of MET and EGFR exon20 insertion responded to crizotinib.BMC medical genomics · 2022Article
- Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers.Virchows Archiv : an international journal of pathology · 2022Article
- Therapeutic advances in metastatic pancreatic cancer: a focus on targeted therapies.Therapeutic advances in medical oncology · 2022Review
- Next-generation Sequencing Reveals Age-dependent Genetic Underpinnings in Lung adenocarcinoma.Journal of Cancer · 2022Article
- NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.Frontiers in oncology · 2022Review
- Comprehensive analysis of oncogenic fusions in mismatch repair deficient colorectal carcinomas by sequential DNA and RNA next generation sequencing.Journal of translational medicine · 2021Article
- Article
- Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults.Current oncology (Toronto, Ont.) · 2021Article
- MLH1/PMS2 Expression Could Tell Classical NTRK Fusion in FluorescenceFrontiers in oncology · 2021Article
- Next-generation sequencing reveals heterogeneous genetic alterations in key signaling pathways of mismatch repair deficient colorectal carcinomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.The American journal of surgical pathology · 2020Review
- DNA Mismatch Repair Deficiency Detection in Colorectal Cancer by a New Microsatellite Instability Analysis System.Interdisciplinary sciences, computational life sciences · 2020Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic fusions are rare in colorectal carcinomas, but may be important for prognosis and therapy. An effective strategy for screening targetable oncogenic fusions in colorectal carcinomas is needed. Here, we investigate molecular genetic alterations in colorectal carcinomas based on their DNA mismatch repair status, and to effectively screen for targetable oncogenic fusions in colorectal carcinomas. In this retrospective study, the initial cohort included 125 consecutive mismatch repair-deficient and 238 randomly selected mismatch repair-proficient colorectal carcinomas diagnosed between July 2015 and December 2017 at Peking Union Medical College Hospital. Targeted sequencing was performed. MLH1 promoter hypermethylation analysis was further employed for subgrouping dMMR colorectal carcinomas. Clinicopathological characteristics, molecular features, and survival outcome of colorectal carcinomas harboring oncogenic fusions were assessed. A multicenter cohort comprised of 227 colorectal carcinomas with dual loss of MLH1/PMS2 was used to validate the efficacy of the proposed screening strategy for oncogenic fusions. Of the 363 patients in the initial cohort, 11(3.0%) harbored oncogenic fusions and were all mismatch repair-deficient colorectal carcinomas with hypermethylated MLH1 and wild-type BRAF and KRAS, comprising 55% (11/20) of this subgroup. These patients with oncogenic fusions showed poorer 3-year cancer-specific survival compared with other Stage III/IV mismatch repair-deficient colorectal carcinoma patients (40% vs. 97%), and significantly higher CD274(PD-L1) expression in tumor cells compared with other dMMR colorectal carcinoma patients (46% vs. 6.1%, P < 0.001). An easy-to-perform and cost-efficient strategy for screening targetable fusions was proposed based on the current molecular testing algorithms for colorectal carcinomas, and validated in an independent multicenter cohort. In conclusion, oncogenic fusions were highly enriched and frequently detected in mismatch repair-deficient colorectal carcinomas with MLH1 hypermethylation and wild-type BRAF and KRAS, and were associated with poor prognosis and high tumor CD274(PD-L1) expression.
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