A newly identified pattern of K-ras mutations at codons 12 and 13 is associated with long-term survival in colorectal cancer

Anthony J. Senagore, Jennifer Thebo Biener

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. Although K-ras mutations reportedly occur in 40% to 60% of all colorectal carcinomas, the relationship between specific mutations and clinical outcome is unclear. The purpose of this study was to assess the frequency and types of K-ras mutations in 89 colorectal cancer patients, comparing groups with short-term (less than 5 years) and long-term (more than 10 years) survival. Methods. The group was divided into four cohorts by survival and modified Dukes classification (Dukes B2 and C2). DNA was extracted from formalin-fixed paraffin-embedded archival material. Mutational status was analyzed using a modification of allele-specific-polymerase chain reaction. Results. Mutations in codon 12 were found in 11.2% of tumors, and 83% of tumors had mutations in codon 13. Gly > Asp accounted for 85.2% of the mutations. Tumors with mutations in both codon 12 and codon 13 occurred significantly more frequently in the long-term (21.3%) versus the short-term (2.4%) survival group. Gly > Asp mutations in either codon were related to long-term survival, and 80% of long-term survivors with mutations in both codons had Gly > Asp mutations in both. Conclusions. Simultaneous mutation in codons 12 and 13 of the K-ras gene appears to be a positive prognostic indicator in colorectal cancer.

Original languageEnglish (US)
Pages (from-to)765-770
Number of pages6
JournalSurgery
Volume122
Issue number4
DOIs
StatePublished - Oct 1997
Externally publishedYes

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Codon
Colorectal Neoplasms
Mutation
Survival
Neoplasms
ras Genes
Paraffin
Formaldehyde
Survivors
Alleles
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Surgery

Cite this

A newly identified pattern of K-ras mutations at codons 12 and 13 is associated with long-term survival in colorectal cancer. / Senagore, Anthony J.; Biener, Jennifer Thebo.

In: Surgery, Vol. 122, No. 4, 10.1997, p. 765-770.

Research output: Contribution to journalArticle

Senagore, Anthony J. ; Biener, Jennifer Thebo. / A newly identified pattern of K-ras mutations at codons 12 and 13 is associated with long-term survival in colorectal cancer. In: Surgery. 1997 ; Vol. 122, No. 4. pp. 765-770.
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abstract = "Background. Although K-ras mutations reportedly occur in 40{\%} to 60{\%} of all colorectal carcinomas, the relationship between specific mutations and clinical outcome is unclear. The purpose of this study was to assess the frequency and types of K-ras mutations in 89 colorectal cancer patients, comparing groups with short-term (less than 5 years) and long-term (more than 10 years) survival. Methods. The group was divided into four cohorts by survival and modified Dukes classification (Dukes B2 and C2). DNA was extracted from formalin-fixed paraffin-embedded archival material. Mutational status was analyzed using a modification of allele-specific-polymerase chain reaction. Results. Mutations in codon 12 were found in 11.2{\%} of tumors, and 83{\%} of tumors had mutations in codon 13. Gly > Asp accounted for 85.2{\%} of the mutations. Tumors with mutations in both codon 12 and codon 13 occurred significantly more frequently in the long-term (21.3{\%}) versus the short-term (2.4{\%}) survival group. Gly > Asp mutations in either codon were related to long-term survival, and 80{\%} of long-term survivors with mutations in both codons had Gly > Asp mutations in both. Conclusions. Simultaneous mutation in codons 12 and 13 of the K-ras gene appears to be a positive prognostic indicator in colorectal cancer.",
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N2 - Background. Although K-ras mutations reportedly occur in 40% to 60% of all colorectal carcinomas, the relationship between specific mutations and clinical outcome is unclear. The purpose of this study was to assess the frequency and types of K-ras mutations in 89 colorectal cancer patients, comparing groups with short-term (less than 5 years) and long-term (more than 10 years) survival. Methods. The group was divided into four cohorts by survival and modified Dukes classification (Dukes B2 and C2). DNA was extracted from formalin-fixed paraffin-embedded archival material. Mutational status was analyzed using a modification of allele-specific-polymerase chain reaction. Results. Mutations in codon 12 were found in 11.2% of tumors, and 83% of tumors had mutations in codon 13. Gly > Asp accounted for 85.2% of the mutations. Tumors with mutations in both codon 12 and codon 13 occurred significantly more frequently in the long-term (21.3%) versus the short-term (2.4%) survival group. Gly > Asp mutations in either codon were related to long-term survival, and 80% of long-term survivors with mutations in both codons had Gly > Asp mutations in both. Conclusions. Simultaneous mutation in codons 12 and 13 of the K-ras gene appears to be a positive prognostic indicator in colorectal cancer.

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