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Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability.
J Clin Oncol. 2007 Sep 20; 25(27):4231-8.JC

Abstract

PURPOSE

Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency has been reported to occur at variable frequencies in inflammatory bowel disease-associated intestinal neoplasias (IBD-Ns). We investigated a large series of IBD-N for associations between MSI and several biologic and clinical parameters related to tumors, patients, and their treatment.

PATIENTS AND METHODS

A total of 277 IBD-Ns in 205 patients were screened for MSI. Biologic and clinical variables of patients with high levels of DNA microsatellite instability high (MSI-H) were collected and compared with those associated with 33 MSI-H non-IBD colorectal cancers (CRCs).

RESULTS

A total of 27 IBD-Ns from 17 patients were found to be MSI-H. Compared with sporadic MSI-H CRCs, patients presented with a younger age at diagnosis, and there was no female predominance and no right-sided predominance. Unlike sporadic MSI-H CRCs, MSI-H IBD-Ns presented with heterogeneous mismatch repair defects involving MLH1, MSH2, MSH6, or PMS2, and a low frequency of MLH1 promoter methylation. They exhibited frequent BRAF mutations and frameshift mutations in genes containing coding repeat sequences.

CONCLUSION

The mechanisms underlying MMR deficiency in MSI-H IBD-Ns are different from those in sporadic MSI-H tumors and seem to be more related to those observed in hereditary MSI-H tumors. However, BRAF mutations were observed in MSI-H IBD-Ns, similar to sporadic MSI-H tumors, but unlike hereditary MSI-H tumors. Finally, the mutational events in target genes for instability are the same in MSI-H IBD-N tumors as in non-IBD sporadic and hereditary colorectal MSI-H cancers, indicating a colon-related repertoire of target gene alterations.

Authors+Show Affiliations

Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service d'Anatomie Pathologique, Paris, France. magali.svrcek@sat.aphp.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17878476

Citation

Svrcek, Magali, et al. "Specific Clinical and Biological Features Characterize Inflammatory Bowel Disease Associated Colorectal Cancers Showing Microsatellite Instability." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 25, no. 27, 2007, pp. 4231-8.
Svrcek M, El-Bchiri J, Chalastanis A, et al. Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability. J Clin Oncol. 2007;25(27):4231-8.
Svrcek, M., El-Bchiri, J., Chalastanis, A., Capel, E., Dumont, S., Buhard, O., Oliveira, C., Seruca, R., Bossard, C., Mosnier, J. F., Berger, F., Leteurtre, E., Lavergne-Slove, A., Chenard, M. P., Hamelin, R., Cosnes, J., Beaugerie, L., Tiret, E., Duval, A., & Fléjou, J. F. (2007). Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 25(27), 4231-8.
Svrcek M, et al. Specific Clinical and Biological Features Characterize Inflammatory Bowel Disease Associated Colorectal Cancers Showing Microsatellite Instability. J Clin Oncol. 2007 Sep 20;25(27):4231-8. PubMed PMID: 17878476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specific clinical and biological features characterize inflammatory bowel disease associated colorectal cancers showing microsatellite instability. AU - Svrcek,Magali, AU - El-Bchiri,Jamila, AU - Chalastanis,Alexandra, AU - Capel,Emilie, AU - Dumont,Sylvie, AU - Buhard,Olivier, AU - Oliveira,Carla, AU - Seruca,Raquel, AU - Bossard,Céline, AU - Mosnier,Jean-François, AU - Berger,Françoise, AU - Leteurtre,Emmanuelle, AU - Lavergne-Slove,Anne, AU - Chenard,Marie-Pierre, AU - Hamelin,Richard, AU - Cosnes,Jacques, AU - Beaugerie,Laurent, AU - Tiret,Emmanuel, AU - Duval,Alex, AU - Fléjou,Jean-François, PY - 2007/9/20/pubmed PY - 2007/10/10/medline PY - 2007/9/20/entrez SP - 4231 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 25 IS - 27 N2 - PURPOSE: Microsatellite instability (MSI) due to mismatch repair (MMR) deficiency has been reported to occur at variable frequencies in inflammatory bowel disease-associated intestinal neoplasias (IBD-Ns). We investigated a large series of IBD-N for associations between MSI and several biologic and clinical parameters related to tumors, patients, and their treatment. PATIENTS AND METHODS: A total of 277 IBD-Ns in 205 patients were screened for MSI. Biologic and clinical variables of patients with high levels of DNA microsatellite instability high (MSI-H) were collected and compared with those associated with 33 MSI-H non-IBD colorectal cancers (CRCs). RESULTS: A total of 27 IBD-Ns from 17 patients were found to be MSI-H. Compared with sporadic MSI-H CRCs, patients presented with a younger age at diagnosis, and there was no female predominance and no right-sided predominance. Unlike sporadic MSI-H CRCs, MSI-H IBD-Ns presented with heterogeneous mismatch repair defects involving MLH1, MSH2, MSH6, or PMS2, and a low frequency of MLH1 promoter methylation. They exhibited frequent BRAF mutations and frameshift mutations in genes containing coding repeat sequences. CONCLUSION: The mechanisms underlying MMR deficiency in MSI-H IBD-Ns are different from those in sporadic MSI-H tumors and seem to be more related to those observed in hereditary MSI-H tumors. However, BRAF mutations were observed in MSI-H IBD-Ns, similar to sporadic MSI-H tumors, but unlike hereditary MSI-H tumors. Finally, the mutational events in target genes for instability are the same in MSI-H IBD-N tumors as in non-IBD sporadic and hereditary colorectal MSI-H cancers, indicating a colon-related repertoire of target gene alterations. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/17878476/Specific_clinical_and_biological_features_characterize_inflammatory_bowel_disease_associated_colorectal_cancers_showing_microsatellite_instability_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2007.10.9744?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -