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Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome.
Gut. 2005 Feb; 54(2):264-7.Gut

Abstract

BACKGROUND AND AIMS

Activating beta-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that beta-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of beta-catenin mutation frequency in each tumour type.

METHODS

Direct sequencing of exon 3 of beta-catenin.

RESULTS

Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (<1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic beta-catenin mutations were identified in 34 MSI+ and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p=0.035) and in both MSI- (p<0.0001) and MSI+ (p=0.008) sporadic cancers. Mutations were more common in higher stage (Dukes' stages C and D) cancers (p=0.001).

CONCLUSION

Exon 3 beta-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+ and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.

Authors+Show Affiliations

Cancer Research UK, Colorectal Cancer Unit, St Mark's Hospital, Harrow, HA1 3UJ, UK.No 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

15647192

Citation

Johnson, V, et al. "Exon 3 Beta-catenin Mutations Are Specifically Associated With Colorectal Carcinomas in Hereditary Non-polyposis Colorectal Cancer Syndrome." Gut, vol. 54, no. 2, 2005, pp. 264-7.
Johnson V, Volikos E, Halford SE, et al. Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome. Gut. 2005;54(2):264-7.
Johnson, V., Volikos, E., Halford, S. E., Eftekhar Sadat, E. T., Popat, S., Talbot, I., Truninger, K., Martin, J., Jass, J., Houlston, R., Atkin, W., Tomlinson, I. P., & Silver, A. R. (2005). Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome. Gut, 54(2), 264-7.
Johnson V, et al. Exon 3 Beta-catenin Mutations Are Specifically Associated With Colorectal Carcinomas in Hereditary Non-polyposis Colorectal Cancer Syndrome. Gut. 2005;54(2):264-7. PubMed PMID: 15647192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome. AU - Johnson,V, AU - Volikos,E, AU - Halford,S E, AU - Eftekhar Sadat,E T, AU - Popat,S, AU - Talbot,I, AU - Truninger,K, AU - Martin,J, AU - Jass,J, AU - Houlston,R, AU - Atkin,W, AU - Tomlinson,I P M, AU - Silver,A R J, PY - 2005/1/14/pubmed PY - 2005/2/8/medline PY - 2005/1/14/entrez SP - 264 EP - 7 JF - Gut JO - Gut VL - 54 IS - 2 N2 - BACKGROUND AND AIMS: Activating beta-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that beta-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of beta-catenin mutation frequency in each tumour type. METHODS: Direct sequencing of exon 3 of beta-catenin. RESULTS: Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (<1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic beta-catenin mutations were identified in 34 MSI+ and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p=0.035) and in both MSI- (p<0.0001) and MSI+ (p=0.008) sporadic cancers. Mutations were more common in higher stage (Dukes' stages C and D) cancers (p=0.001). CONCLUSION: Exon 3 beta-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+ and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation. SN - 0017-5749 UR - https://www.unboundmedicine.com/medline/citation/15647192/Exon_3_beta_catenin_mutations_are_specifically_associated_with_colorectal_carcinomas_in_hereditary_non_polyposis_colorectal_cancer_syndrome_ L2 - https://gut.bmj.com/lookup/pmidlookup?view=long&amp;pmid=15647192 DB - PRIME DP - Unbound Medicine ER -