High microsatellite instability (MSI-H) colorectal carcinoma: A brief review of predictive biomarkers in the era of personalized medicine
Open accessAbstract
Approximately 15 % of colorectal carcinomas (CRC) display high level microsatellite instability (MSI-H) due to either a germline mutation in one of the genes responsible for DNA mismatch repair (Lynch syndrome, 3 %) or somatic inactivation of the same pathway, most commonly through hypermethylation of the MLH1 gene (sporadic MSI-H, 12 %). Although heterogeneous, MSI-H colorectal carcinomas as a group show some distinct biologic characteristics when compared to CRC with stable or low level microsatellite instability. In the present review we will highlight therapeutically relevant characteristics of MSI-H tumors which could lead to specific responses to some conventional chemotherapy or novel targeted therapy agents.
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The presence of microsatellite instability indicates deficient mismatch repair and hypermutability of cells.
“Therefore, the presence of MSI indicates dMMR and hypermutability of cells [35].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [35]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628 · see citing works
Siegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854 · see citing works
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377 · see citing works
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499 · see citing works
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · see citing works
A microRNA expression signature of human solid tumors defines cancer gene targets
Volinia, S., Calin, G. A., Liu, C.-G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510565103 · Cited by 5,697 · see citing works
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231 · see citing works
The consensus molecular subtypes of colorectal cancer
Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015) · Nature Medicine · doi:10.1038/nm.3967 · Cited by 5,170 · see citing works
Taube, J. M., Klein, A., Brahmer, J. R., Xu, H., Pan, X., Kim, J. H., Chen, L., Pardoll, D. M., Topalian, S. L., & Anders, R. A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3271 · Cited by 2,324 · see citing works
Ribic, C. M., Sargent, D. J., Moore, M. J., Thibodeau, S. N., French, A. J., Goldberg, R. M., Hamilton, S. R., Laurent-Puig, P., Gryfe, R., Shepherd, L. E., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022289 · Cited by 2,160 · see citing works
Weisenberger, D. J., Siegmund, K. D., Campan, M., Young, J. P., Long, T. I., Faasse, M. A., Kang, G. H., Widschwendter, M., Weener, D., Buchanan, D. D., et al. (2006) · Nature Genetics · doi:10.1038/ng1834 · Cited by 1,990 · see citing works
Landon, M., Saam, J. R., Brown, K. L., Moyes, K., Evans, B. A., & WENSTRUP, R. J. (2015) · Oncology · doi:10.1159/000430097 · Cited by 1,943 · see citing works
Llosa, N. J., Cruise, M., Tam, A., Wicks, E. C., Hechenbleikner, E. M., Taube, J. M., Blosser, R. L., Fan, H., Wang, H., Luber, B. S., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0863 · Cited by 1,487 · see citing works
Anemia as an independent prognostic factor for survival in patients with cancer
Caro, J. J., Salas, M., Ward, A., & Goss, G. D. (2001) · Cancer · doi:10.1002/1097-0142(20010615)91:12 · Cited by 947 · see citing works
Ligtenberg, M. J. L., Kuiper, R. P., Chan, T. L., Goossens, M., Hebeda, K. M., Voorendt, M., Lee, T. Y. H., Bodmer, D., Hoenselaar, E., Hendriks-Cornelissen, S. J. B., et al. (2009) · Nature Genetics · doi:10.1038/ng.283 · Cited by 818 · see citing works
Kaina, B., Christmann, M., Naumann, S. C., & Roos, W. P. (2007) · DNA repair · doi:10.1016/j.dnarep.2007.03.008 · Cited by 666 · see citing works
The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through Its Interaction with MutSα
Li, F., Mao, G., Tong, D., Huang, J., Gu, L., Yang, W., & Li, G. (2013) · Cell · doi:10.1016/j.cell.2013.03.025 · Cited by 591 · see citing works
Sunshine, J. C., & Taube, J. M. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.05.011 · Cited by 562 · see citing works
The Clinical Phenotype of Lynch Syndrome Due to Germ-Line PMS2 Mutations
Senter, L. A., Clendenning, M., Sotamaa, K., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.04.026 · Cited by 552 · see citing works
Gatalica, Z., Snyder, C., Maney, T., Ghazalpour, A., Holterman, D. A., Xiao, N., Overberg, P., Rose, I., Basu, G. D., Vranić, S., et al. (2014) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-14-0654 · Cited by 522 · see citing works
Self-citationHunter, C., Smith, R., Cahill, D. P., Stephens, P., Stevens, C., Teague, J. W., Greenman, C., Edkins, S., Bignell, G. R., Davies, H. R., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0127 · Cited by 431 · see citing works
Modulation of mismatch repair and genomic stability by miR-155
Valeri, N., Gasparini, P., Fabbri, M., Braconi, C., Veronese, A., Lovat, F., Adair, B., Vannini, I., Fanini, F., Bottoni, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002472107 · Cited by 347 · see citing works
Parsons, M. T., Buchanan, D. D., Thompson, B. A., Young, J. P., & Spurdle, A. B. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100714 · Cited by 311 · see citing works
Antagonists of PD-1 and PD-L1 in Cancer Treatment
Lipson, E. J., Forde, P. M., Hammers, H.-J., Emens, L. A., Taube, J. M., & Topalian, S. L. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.05.013 · Cited by 306 · see citing works
Guetz, G. D., Schischmanoff, P. O., Nicolas, P., Perret, G. Y., Morère, J., & Uzzan, B. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2009.04.018 · Cited by 291 · see citing works
Genetic and epigenetic biomarkers for diagnosis, prognosis and treatment of colorectal cancer
Coppedè, F. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i4.943 · Cited by 264 · see citing works
Taube, J. M., Young, G. D., McMiller, T. L., Chen, S., Salas, J. T., Pritchard, T. S., Xu, H., Meeker, A. K., Fan, J., Cheadle, C., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0244 · Cited by 248 · see citing works
Microsatellite instability: an update
Yamamoto, H., & Imai, K. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1474-0 · Cited by 247 · see citing works
Timmermann, B., Kerick, M., Roehr, C., Fischer, A., Isau, M., Boerno, S. T., Wunderlich, A., Barmeyer, C., Seemann, P., Koenig, J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015661 · Cited by 243 · see citing works
Mismatch repair deficient colorectal cancer in the era of personalized treatment
Hewish, M., Lord, C. J., Martin, S. A., Cunningham, D., & Ashworth, A. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.18 · Cited by 233 · see citing works
Mechanisms of tolerance to DNA damaging therapeutic drugs
Karran, P. (2001) · Carcinogenesis · doi:10.1093/carcin/22.12.1931 · Cited by 226 · see citing works
Relevance, Pathogenesis, and Testing Algorithm for Mismatch Repair–Defective Colorectal Carcinomas
Funkhouser, W. K., Lubin, I. M., Monzon, F. A., Zehnbauer, B. A., Evans, J. P., Ogino, S., & Nowak, J. A. (2012) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2011.11.001 · Cited by 188 · see citing works
The CpG island methylator phenotype (CIMP) in colorectal cancer.
Mojarad, E. N., Kuppen, P. J. K., Aghdaei, H. A., & Zali, M. R. (2013) · Europe PMC (PubMed Central) · Cited by 164 · see citing works
Thymidylate Synthase: A Critical Target for Cancer Chemotherapy
Rose, M. G., Farrell, M., & Schmitz, J. C. (2002) · Clinical Colorectal Cancer · doi:10.3816/ccc.2002.n.003 · Cited by 150 · see citing works
Koopman, M., Venderbosch, S., van Tinteren, H., Ligtenberg, M. J. L., Nagtegaal, I. D., van Krieken, J. H., & Punt, C. J. A. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2009.04.017 · Cited by 91 · see citing works
Pathology of the hereditary colorectal carcinoma
Gatalica, Z., & Torlakovic, E. (2007) · Familial Cancer · doi:10.1007/s10689-007-9146-8 · Cited by 70 · see citing works
Self-citationTaube, J. M. (2014) · OncoImmunology · doi:10.4161/21624011.2014.963413 · Cited by 68 · see citing works
Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer
Gonzalo, V., Lozano, J. J., Muñoz, J., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008777 · Cited by 66 · see citing works
Anti program death-1/anti program death-ligand 1 in digestive cancers
Guillebon, É. D. (2015) · World Journal of Gastrointestinal Oncology · doi:10.4251/wjgo.v7.i8.95 · Cited by 53 · see citing works
Chemotherapy of MMR-deficient colorectal cancer
Devaud, N., & Gallinger, S. (2013) · Familial Cancer · doi:10.1007/s10689-013-9633-z · Cited by 52 · see citing works
Li, G. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1870 · Cited by 42 · see citing works
Dienstmann, R., Salazar, R., & Tabernero, J. (2014) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2014.34.91 · Cited by 38 · see citing works
Jensen, S. A., Vainer, B., Kruhøffer, M., et al. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-25 · Cited by 37 · see citing works
Role of MGMT as biomarker in colorectal cancer
Inno, A. (2014) · World Journal of Clinical Cases · doi:10.12998/wjcc.v2.i12.835 · Cited by 36 · see citing works
Evidence for the role of aberrant DNA methylation in the pathogenesis of Lynch syndrome adenomas
Kaz, A. M., Kim, Y., Dzieciatkowski, S., Lynch, H. T., Watson, P. A., Washington, M. K., Li, L., & Grady, W. M. (2007) · International Journal of Cancer · doi:10.1002/ijc.22544 · Cited by 35 · see citing works
Shacham‐Shmueli, E., Beny, A., Geva, R., Blachar, A., Figer, A., & Aderka, D. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.0242 · Cited by 33 · see citing works
Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer
Pietrantonio, F., de Braud, F., Milione, M., Maggi, C., Iacovelli, R., Dotti, K. F., Perrone, F., Tamborini, E., Caporale, M., Berenato, R., et al. (2015) · Targeted Oncology · doi:10.1007/s11523-015-0397-2 · Cited by 28 · see citing works
Rømer, M. U., Jensen, N. F., Nielsen, S. L., Müller, S., Nielsen, K. V., Nielsen, H. J., & Brünner, N. (2011) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2011.638393 · Cited by 28 · see citing works
Maccaroni, E., Bracci, R., Giampieri, R., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5395 · Cited by 26 · see citing works
Sønderstrup, I. M. H., Nygård, S. B., Poulsen, T. S., et al. (2015) · Molecular Oncology · doi:10.1016/j.molonc.2015.02.009 · Cited by 25 · see citing works
Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review
Li, Y., Lyu, Z., Zhao, L., et al. (2015) · Tumor Biology · doi:10.1007/s13277-014-2752-9 · Cited by 24 · see citing works
Maurel, J., & Postigo, A. A. (2015) · Current Cancer Drug Targets · doi:10.2174/156800961508151001102822 · Cited by 24 · see citing works
Bendardaf, R., Lamlum, H., Ristamäki, R., et al. (2008) · Acta Oncologica · doi:10.1080/02841860701678753 · Cited by 15 · see citing works
Negri, F., Azzoni, C., Bottarelli, L., et al. (2013) · PubMed · Cited by 11 · see citing works
Zheng, C., Jin, C., Ye, L., et al. (2015) · Tumor Biology · doi:10.1007/s13277-015-3254-0 · Cited by 10 · see citing works
Dionigi, G., Bianchi, V., Villa, F., et al. (2007) · Surgical Oncology · doi:10.1016/j.suronc.2007.10.018 · Cited by 7 · see citing works
Therapeutic biomarker differences between MSI-H and MSS colorectal cancers.
Gatalica, Z., Vijayvergia, N., Vranić, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.33.15_suppl.3597 · Cited by 3 · see citing works
Self-citationGatalica, Z., Vranić, S., Basu, G. D., et al. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu333.72 · Cited by 1 · see citing works
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- [5]Cheng L (2009) Molecular genetic pathology, 1st edn. Humana Press, New Jersey, pp 455–457.
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- Authors
- Gatalica, Z., Vranic, S., Xiu, J., Swensen, J., & Reddy, S.
- Affiliations
- Caris Life Sciences (United States) (US)
- Corresponding author
- Gatalica, Zoran
- Venue
- Familial Cancer
- Published
- 2016-02-13
- Volume
- 15
- Issue
- 3
- Pages
- 405-412
- ISSN
- 1389-9600 (ISSN-L)
- 1573-7292
- PMC
- PMC4901118
- OpenAlex
- W2262022146
- Cited by
- 141
- References
- 59
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 15 · 2023: 10 · 2022: 16 · 2021: 16 · 2020: 20 · 2019: 17 · 2018: 19 · 2017: 9 · 2016: 5
- FWCI
- 15.15
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Familial Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- microsatellite instability, predictive biomarkers, personalized medicine, DNA mismatch repair, Lynch syndrome, MLH1 hypermethylation, somatic inactivation, chemotherapy response, targeted therapy
- MeSH terms
- MutL Protein Homolog 1, Antineoplastic Agents, Humans, Promoter Regions, Genetic, Biomarkers, Tumor, Colorectal Neoplasms, Biomarkers, Germ-Line Mutation, DNA Methylation, DNA Repair Enzymes, Microsatellite Instability, DNA Mismatch Repair, Precision Medicine, Molecular Targeted Therapy
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