- •Metastatic colorectal cancers with sporadic or inherited MMR deficiency display distinct natural histories.
- •A algorithm combining MMR protein expression, BRAF mutation and MLH1 methylation is mandatory to properly determine the mechanism of MMR deficiency.
- •A better characterisation of dMMR CRCs is needed to determine whether therapeutic agents efficacy differs depending on the origin of the MMR deficiency.
Patients and methods
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- Immunotherapy and patients treated for cancer with microsatellite instability.Bull Cancer (Paris). 2017; 104: 42-51https://doi.org/10.1016/j.bulcan.2016.11.006
- A tailored approach to BRAF and MLH1 methylation testing in a universal screening program for Lynch syndrome.Mod Pathol. 2017;
- Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch Syndrome (HNPCC).J Med Genet. 2014; 51: 789-796https://doi.org/10.1136/jmedgenet-2014-102552
- Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification.J Med Genet. 2012; 49: 151-157https://doi.org/10.1136/jmedgenet-2011-100714
- Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability.Cancer Res. 1998; 58: 3455-3460
- Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.J Clin Oncol. 2010; 28: 3219-3226https://doi.org/10.1200/JCO.2009.27.1825
- Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study.J Clin Oncol. 2015; 33: 4176-4187https://doi.org/10.1200/JCO.2015.63.4238
- Efficacy of adjuvant chemotherapy in colon cancer with microsatellite instability: a large multicenter AGEO study.J Natl Cancer Inst. 2016; 108: djv438https://doi.org/10.1093/jnci/djv438
- DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy.J Natl Cancer Inst. 2011; 103: 863-875https://doi.org/10.1093/jnci/djr153
- Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy.Anticancer Res. 2003; 23: 1773-1777
- Microsatellite instability and sensitivity to FOLFOX treatment in metastatic colorectal cancer.Anticancer Res. 2007; 27: 2715-2719
- Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.Cancer. 2011; 117: 4623-4632https://doi.org/10.1002/cncr.26086
- Deficient mismatch repair system in patients with sporadic advanced colorectal cancer.Br J Cancer. 2009; 100: 266-273https://doi.org/10.1038/sj.bjc.6604867
- Metastatic pattern of stage IV colorectal cancer with high-frequency microsatellite instability as a prognostic factor.Anticancer Res. 2017; 37: 239-247
- Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies.Clin Cancer Res. 2014; 20: 5322-5330https://doi.org/10.1158/1078-0432.CCR-14-0332
- PD-1 blockade in tumors with mismatch-repair deficiency.N Engl J Med. 2015; 372: 2509-2520https://doi.org/10.1056/NEJMoa1500596
- Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.Lancet Oncol. 2017; 18: 1182-1191https://doi.org/10.1016/S1470-2045(17)30422-9
- Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US multi-society task force on colorectal cancer.Gastroenterology. 2014; 147: 502-526https://doi.org/10.1053/j.gastro.2014.04.001
- Hereditary colorectal cancer syndromes: American Society of Clinical Oncology clinical practice guideline endorsement of the familial risk–colorectal cancer: European Society for Medical Oncology clinical practice guidelines.J Clin Oncol. 2015; 33: 209-217https://doi.org/10.1200/JCO.2014.58.1322
- Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer.Clin Cancer Res. 2008; 14: 3408-3415https://doi.org/10.1158/1078-0432.CCR-07-1489
- Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: a post hoc analysis of the PETACC-8 trial.JAMA Oncol. 2016; 2: 643https://doi.org/10.1001/jamaoncol.2015.5225
- Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H).Ann Oncol. 2014; 25: 1032-1038https://doi.org/10.1093/annonc/mdu100
- Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.J Clin Oncol. 2010; 28: 466-474https://doi.org/10.1200/JCO.2009.23.3452
- Identification of a poor-prognosis BRAF-mutant–like population of patients with colon cancer.J Clin Oncol. 2012; 30: 1288-1295https://doi.org/10.1200/JCO.2011.39.5814
- The consensus molecular subtypes of colorectal cancer.Nat Med. 2015; 21: 1350-1356https://doi.org/10.1038/nm.3967
- Familial risk-colorectal cancer: ESMO clinical practice guidelines.Ann Oncol. 2013; 24: vi73-vi80https://doi.org/10.1093/annonc/mdt209
- Programmed death-1 blockade in mismatch repair deficient colorectal cancer.J Clin Oncol. 2016; 34 (suppl; abstr 103)