Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Microsatellite instability in colorectal cancer—the stable evidence


Microsatellite instability (MSI) is the molecular fingerprint of a deficient mismatch repair system. Approximately 15% of colorectal cancers (CRC) display MSI owing either to epigenetic silencing of MLH1 or a germline mutation in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2. Methods to detect MSI are well established and routinely incorporated into clinical practice. A clinical and molecular profile of MSI tumors has been described, leading to the concept of an MSI phenotype in CRC. Studies have confirmed that MSI tumors have a better prognosis than microsatellite stable CRC, but MSI cancers do not necessarily have the same response to the chemotherapeutic strategies used to treat microsatellite stable tumors. Specifically, stage II MSI tumors might not benefit from 5-fluorouracil-based adjuvant chemotherapy regimens. New data suggest possible advantages of irinotecan-based regimens, but these findings require further clarification. Characterization of the molecular basis of MSI in CRC is underway and initial results show that mutations in genes encoding kinases and candidate genes with microsatellite tracts are over-represented in MSI tumors. Transcriptome expression profiles of MSI tumors and systems biology approaches are providing the opportunity to develop targeted therapeutics for MSI CRC.

Key Points

  • Microsatellite instability (MSI) is present in approximately 15% of colorectal cancers (CRC), which are mostly nonfamilial (sporadic) and caused by hypermethylation of the MLH1 promoter

  • Approximately 2–3% of all CRC are caused by germline mutations in one of the mismatch repair genes (MLH1, MSH2, MSH6 and PMS2)

  • The MSI phenotype is characterized by right-sided location, low pathological stage, mucinous presentation, tumor-infiltrating lymphocytes, absence of necrotic cellular debris and the presence of a Crohn-like nodular infiltrate

  • MSI tumors have a good prognosis and reduced likelihood of metastasis compared with microsatellite stable tumors, which highlights the value of MSI as a prognostic marker in CRC

  • Although 5-fluorouracil-based chemotherapy is the gold standard for CRC, this drug offers little benefit in early MSI CRC—irinotecan-based regimens and other drugs may hold promise, and are being studied in MSI CRC

  • Transcriptome expression studies that characterize MSI tumors and cell lines have identified unique attributes of MSI cancers, and systems biology tools and other approaches enable investigation of targeted therapies

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Model of the proposed mechanism of mismatch repair proteins, illustrating patterns of clinically relevant heterodimerization.
Figure 2: Capillary electrophoresis of an MSI cancer.
Figure 3: Immunohistochemical patterns of mismatch repair proteins in colorectal cancers.
Figure 4: CRC progression models and therapeutic targets in MSI and MSS CRC.


  1. 1

    Aaltonen, L. A. et al. Clues to the pathogenesis of familial colorectal cancer. Science 260, 812–816 (1993).

    CAS  Google Scholar 

  2. 2

    Ionov, Y., Peinado, M. A., Malkhosyan, S., Shibata, D. & Perucho, M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363, 558–561 (1993).

    CAS  Article  Google Scholar 

  3. 3

    Thibodeau, S. N., Bren, G. & Schaid, D. Microsatellite instability in cancer of the proximal colon. Science 260, 816–819 (1993).

    CAS  Article  Google Scholar 

  4. 4

    Aaltonen, L. A. et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N. Engl. J. Med. 338, 1481–1487 (1998).

    CAS  Google Scholar 

  5. 5

    Hampel, H. et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N. Engl. J. Med. 352, 1851–1860 (2005).

    CAS  PubMed  Google Scholar 

  6. 6

    Hendriks, Y. M. et al. Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians. CA Cancer J. Clin. 56, 213–225 (2006).

    Google Scholar 

  7. 7

    Jiricny, J. The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 7, 335–346 (2006).

    CAS  Google Scholar 

  8. 8

    Hoeijmakers, J. H. Genome maintenance mechanisms for preventing cancer. Nature 411, 366–374 (2001).

    CAS  Google Scholar 

  9. 9

    Boland, C. R. et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 58, 5248–5257 (1998).

    CAS  PubMed  Google Scholar 

  10. 10

    Pal, T., Permuth-Wey, J., Kumar, A. & Sellers, T. A. Systematic review and meta-analysis of ovarian cancers: estimation of microsatellite-high frequency and characterization of mismatch repair deficient tumor histology. Clin. Cancer Res. 14, 6847–6854 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Vogelstein, B. & Kinzler, K. W. in The Genetic Basis of Human Cancer (McGraw-Hill Medical, New York, 2002).

    Google Scholar 

  12. 12

    Salovaara, R. et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J. Clin. Oncol. 18, 2193–2200 (2000).

    CAS  Google Scholar 

  13. 13

    Ligtenberg, M. J. et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1. Nat. Genet. 41, 112–117 (2009).

    CAS  Google Scholar 

  14. 14

    Chen, S. et al. Prediction of germline mutations and cancer risk in the Lynch syndrome. JAMA 296, 1479–1487 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Stoffel, E. et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology 137, 1621–1627 (2009).

    PubMed  PubMed Central  Google Scholar 

  16. 16

    Herman, J. G. et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl Acad. Sci. USA 95, 6870–6875 (1998).

    CAS  Google Scholar 

  17. 17

    Gryfe, R. et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N. Engl. J. Med. 342, 69–77 (2000).

    CAS  Google Scholar 

  18. 18

    Piñol, V. et al. Accuracy of revised Bethesda guidelines, microsatellite instability, and immunohistochemistry for the identification of patients with hereditary nonpolyposis colorectal cancer. JAMA 293, 1986–1994 (2005).

    Google Scholar 

  19. 19

    Roth, A. D. et al. Stage-specific prognostic value of molecular markers in colon cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60–00 trial [abstract]. J. Clin. Oncol. 27, a4002 (2009).

    Google Scholar 

  20. 20

    Koopman, M. et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br. J. Cancer 100, 266–273 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Ashktorab, H. et al. High incidence of microsatellite instability in colorectal cancer from African Americans. Clin. Cancer Res. 9, 1112–1117 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Kumar, K. et al. Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans. Clin. Cancer Res. 15, 1155–1161 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Soliman, A. S. et al. Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients. Br. J. Cancer 85, 1037–1046 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    Gruber, S. B. New developments in Lynch syndrome (hereditary nonpolyposis colorectal cancer) and mismatch repair gene testing. Gastroenterology 130, 577–587 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Laghi, L., Bianchi, P. & Malesci, A. Differences and evolution of the methods for the assessment of microsatellite instability. Oncogene 27, 6313–6321 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Umar, A. et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J. Natl Cancer Inst. 96, 261–268 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27

    Vogelstein, B. et al. Allelotype of colorectal carcinomas. Science 244, 207–211 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29

    Duval, A. & Hamelin, R. Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability. Cancer Res. 62, 2447–2454 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002).

    CAS  Google Scholar 

  31. 31

    Rajagopalan, H. et al. Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. Nature 418, 934 (2002).

    CAS  PubMed  Google Scholar 

  32. 32

    Oliveira, C. et al. BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency. Oncogene 22, 9192–9196 (2003).

    CAS  Google Scholar 

  33. 33

    Domingo, E. et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J. Med. Genet. 41, 664–668 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34

    Bessa, X. et al. A prospective, multicenter, population-based study of BRAF mutational analysis for Lynch syndrome screening. Clin. Gastroenterol. Hepatol. 6, 206–214 (2008).

    CAS  Google Scholar 

  35. 35

    Deng, G. et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. Clin. Cancer Res. 10, 191–195 (2004).

    CAS  Google Scholar 

  36. 36

    McGivern, A. et al. Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer. Fam. Cancer 3, 101–107 (2004).

    CAS  Google Scholar 

  37. 37

    Wang, L. et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 63, 5209–5212 (2003).

    CAS  Google Scholar 

  38. 38

    Andreyev, H. J., Norman, A. R., Cunningham, D., Oates, J. R. & Clarke, P. A. Kirsten ras mutations in patients with colorectal cancer: the multicenter “RASCAL” study. J. Natl Cancer Inst. 90, 675–684 (1998).

    CAS  Google Scholar 

  39. 39

    Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489–501 (2002).

    CAS  Google Scholar 

  40. 40

    Samuels, Y. et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554 (2004).

    CAS  PubMed  Google Scholar 

  41. 41

    Barault, L. et al. Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int. J. Cancer 1 22, 2255–2259 (2008).

    Google Scholar 

  42. 42

    Benvenuti, S. et al. PIK3CA cancer mutations display gender and tissue specificity patterns. Hum. Mutat. 29, 284–288 (2008).

    CAS  Google Scholar 

  43. 43

    Frattini, M. et al. Phosphatase protein homologue to tensin expression and phosphatidylinositol-3 phosphate kinase mutations in colorectal cancer. Cancer Res. 65, 11227 (2005).

    CAS  Google Scholar 

  44. 44

    Kato, S. et al. PIK3CA mutation is predictive of poor survival in patients with colorectal cancer. Int. J. Cancer 121, 1771–1778 (2007).

    CAS  Google Scholar 

  45. 45

    Sartore-Bianchi, A. et al. PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res. 69, 1851–1857 (2009).

    CAS  Google Scholar 

  46. 46

    Ogino, S. et al. PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J. Clin. Oncol. 27, 1477–1484 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47

    Abubaker, J. et al. Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population. Oncogene 27, 3539–3545 (2008).

    CAS  PubMed  Google Scholar 

  48. 48

    Parsons, D. W. et al. Colorectal cancer: mutations in a signalling pathway. Nature 436, 792 (2005).

    CAS  PubMed  Google Scholar 

  49. 49

    Goel, A. et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 64, 3014–3021 (2004).

    CAS  Google Scholar 

  50. 50

    Banerjea, A. et al. Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity. Mol. Cancer 3, 21 (2004).

    PubMed  PubMed Central  Google Scholar 

  51. 51

    Koinuma, K. et al. Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas. Int. J. Cancer 108, 237–242 (2004).

    CAS  Google Scholar 

  52. 52

    Vilar, E. et al. Gene expression patterns in mismatch repair-deficient colorectal cancers highlight the potential therapeutic role of inhibitors of the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway. Clin. Cancer Res. 15, 2829–2839 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Watanabe, T. et al. Distal colorectal cancers with microsatellite instability (MSI) display distinct gene expression profiles that are different from proximal MSI cancers. Cancer Res. 66, 9804–9808 (2006).

    CAS  Google Scholar 

  54. 54

    Kruhøffer, M. et al. Gene expression signatures for colorectal cancer microsatellite status and HNPCC. Br. J. Cancer 92, 2240–2248 (2005).

    PubMed  PubMed Central  Google Scholar 

  55. 55

    Giacomini, C. P. et al. A gene expression signature of genetic instability in colon cancer. Cancer Res. 65, 9200–9205 (2005).

    CAS  Google Scholar 

  56. 56

    Michiels, S., Koscielny, S. & Hill, C. Interpretation of microarray data in cancer. Br. J. Cancer 96, 1155–1158 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57

    Cardoso, F. et al. Clinical application of the 70-gene profile: the MINDACT trial. J. Clin. Oncol. 26, 729–735 (2008).

    Google Scholar 

  58. 58

    Sparano, J. A. & Paik, S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J. Clin. Oncol. 26, 721–728 (2008).

    Google Scholar 

  59. 59

    Greenson, J. K. et al. Phenotype of microsatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability. Am. J. Surg. Pathol. 27, 563–570 (2003).

    Google Scholar 

  60. 60

    Jorissen, R. N. et al. DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable colorectal cancers. Clin. Cancer Res. 14, 8061–8069 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Poynter, J. N. et al. Associations between smoking, alcohol consumption, and colorectal cancer, overall and by tumor microsatellite instability status. Cancer Epidemiol. Biomarkers Prev. 18, 2745–2750 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Ribic, C. M. et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N. Engl. J. Med. 349, 247–257 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Watanabe, T. et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N. Engl. J. Med. 344, 1196–1206 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Popat, S., Hubner, R. & Houlston, R. S. Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol. 23, 609–618 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65

    Carethers, J. M. et al. Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 117, 123–131 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. 66

    Elsaleh, H. et al. Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355, 1745–1750 (2000).

    CAS  PubMed  Google Scholar 

  67. 67

    Hemminki, A., Mecklin, J. P., Järvinen, H., Aaltonen, L. A. & Joensuu, H. Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology 119, 921–928 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68

    Liang, J. T. et al. High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection. Int. J. Cancer 101, 519–525 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69

    Benatti, P. et al. Microsatellite instability and colorectal cancer prognosis. Clin Cancer Res. 11, 8332–8340 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Jover, R. et al. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Gut 55, 848–855 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Kim, G. P. et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J. Clin. Oncol. 25, 767–772 (2007).

    CAS  Google Scholar 

  72. 72

    Lamberti, C. et al. Microsatellite instability did not predict individual survival of unselected patients with colorectal cancer. Int. J. Colorectal Dis. 22, 145–152 (2007).

    CAS  Google Scholar 

  73. 73

    Sargent, D. J. et al. Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): A pooled molecular reanalysis of randomized chemotherapy trials [abstract]. J. Clin. Oncol. 26, a4008 (2008).

    Google Scholar 

  74. 74

    Des Guetz, G. et al. Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. Eur. J. Cancer 45, 1890–1896 (2009).

    CAS  Google Scholar 

  75. 75

    Baddi, L. & Benson, A. III. Adjuvant therapy in stage II colon cancer: current approaches. Oncologist 10, 325–331 (2005).

    Google Scholar 

  76. 76

    Van Rijnsoever, M., Elsaleh, H., Joseph, D., McCaul, K. & Iacopetta, B. CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clin. Cancer Res. 9, 2898–2903 (2003).

    CAS  Google Scholar 

  77. 77

    Nagasaka, T. et al. Hypermethylation of O6-methylguanine-DNA methyltransferase promoter may predict nonrecurrence after chemotherapy in colorectal cancer cases. Clin. Cancer Res. 9, 5306–5312 (2003).

    CAS  Google Scholar 

  78. 78

    Vilar, E. et al. Microsatellite instability due to hMLH1 deficiency is associated with increased cytotoxicity to irinotecan in human colorectal cancer cell lines. Br. J. Cancer 99, 1607–1612 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Magrini, R. et al. Cellular effects of CPT-11 on colon carcinoma cells: dependence on p53 and hMLH1 status. Int. J. Cancer 101, 23–31 (2002).

    CAS  Google Scholar 

  80. 80

    Jacob, S., Aguado, M., Fallik, D. & Praz, F. The role of the DNA mismatch repair system in the cytotoxicity of the topoisomerase inhibitors camptothecin and etoposide to human colorectal cancer cells. Cancer Res. 61, 6555–6562 (2001).

    CAS  Google Scholar 

  81. 81

    Rodriguez, R. et al. Thymidine selectively enhances growth suppressive effects of camptothecin/irinotecan in MSI+ cells and tumors containing a mutation of MRE11. Clin. Cancer Res. 14, 5476–5483 (2008).

    CAS  Google Scholar 

  82. 82

    Pommier, Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat. Rev. Cancer 6, 789–802 (2006).

    CAS  PubMed  Google Scholar 

  83. 83

    Giannini, G. et al. Mutations of an intronic repeat induce impaired MRE11 expression in primary human cancer with microsatellite instability. Oncogene 23, 2640–2647 (2004).

    CAS  Google Scholar 

  84. 84

    Miquel, C. et al. Frequent alteration of DNA damage signalling and repair pathways in human colorectal cancers with microsatellite instability. Oncogene 26, 5919–5926 (2007).

    CAS  Google Scholar 

  85. 85

    Fallik, D. et al. Microsatellite instability is a predictive factor of the tumor response to irinotecan in patients with advanced colorectal cancer. Cancer Res. 63, 5738–5744 (2003).

    CAS  Google Scholar 

  86. 86

    Bertagnolli, M. M. et al. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J. Clin. Oncol. 27, 1814–1821 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Tejpar, S. et al. Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial) [abstract]. J. Clin. Oncol. 27, a4001 (2009).

    Google Scholar 

  88. 88

    Koopman, M. et al. Sequential versus combination chemotherpay with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet 370, 135–142 (2007).

    CAS  Google Scholar 

  89. 89

    Des Guetz, G. et al. Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer. A systematic review and meta-analysis. Anticancer Res. 29, 1615–1620 (2009).

    CAS  Google Scholar 

  90. 90

    Swanton, C. & Caldas, C. Molecular classification of solid tumours: towards pathway-driven therapeutics. Br. J. Cancer 100, 1517–1522 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91

    Engstrom, P. F. et al. NCCN Clinical Practice Guideline in Oncology: colon cancer. J. Natl Compr. Canc. Netw. 7, 778–831 (2009).

    PubMed  PubMed Central  Google Scholar 

  92. 92

    Vilar, E. et al. Preclinical testing of the PARP inhibitor ABT-888 in microsatellite instable colorectal cancer [abstract]. J. Clin. Oncol. 27, a11028 (2009).

    Google Scholar 

  93. 93

    Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917–921 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Ropero, S. et al. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition. Nat. Genet. 3 8, 566–569 (2006).

    Google Scholar 

Download references


E. Vilar was supported by a fellowship from “la Caixa”, Barcelona, Spain. S. B. Gruber's laboratory work is supported by NCI grant 1R01CA81488 and by the University of Michigan Comprehensive Cancer Center Core Support grant NIH 5P30CA46592.

Author information



Corresponding author

Correspondence to Stephen B. Gruber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vilar, E., Gruber, S. Microsatellite instability in colorectal cancer—the stable evidence. Nat Rev Clin Oncol 7, 153–162 (2010).

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing