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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Vaughn, Cecily P. Zobell, Scott D. Furtado, Larissa V. Baker, Christine L. Samowitz, Wade S. |
| Description | Country affiliation: United States Author Affiliation: Vaughn CP ( ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA.) |
| Abstract | Mutational analysis of KRAS codons 12 and 13 is standard for patients with metastatic colorectal cancer since mutations in these codons predict lack of response to anti-EGFR therapies. However, even among patients whose tumors are wildtype for KRAS codons 12 and 13, only a subset respond to therapy. Since additional activating mutations downstream of EGFR may also play a role in treatment resistance, we sought to establish the frequency of these mutations. We evaluated 2121 colorectal tumors for mutations in codons 12 and 13 of the KRAS gene. A subset of these samples, comprised of 513 samples wildtype for KRAS codons 12 and 13, were tested for mutations in codons 61 and 146 of KRAS, codon 600 of BRAF, and codons 12, 13, and 61 of NRAS. Mutation status was determined by targeted pyrosequencing. Mutations in KRAS codon 12 or 13 were identified in 900/2121 (42.4%) samples. Of the 513 wildtype samples tested for additional mutations, 78 samples were mutant for BRAF, 19 for KRAS codon 61, 17 for KRAS codon 146, and 26 for NRAS. In total, 140/513 (27.3%) tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes. While further study is needed to determine the full therapeutic implications of mutations in these codons, mutational testing of these codons may be useful for identifying a significant proportion of patients who may also be resistant to anti-EGFR therapies. |
| File Format | HTM / HTML |
| ISSN | 10452257 |
| Issue Number | 5 |
| Volume Number | 50 |
| e-ISSN | 10982264 |
| Journal | Genes, Chromosomes and Cancer |
| Language | English |
| Publisher | Wiley-Liss |
| Publisher Date | 2011-05-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Molecular Biology Discipline Oncology Colorectal Neoplasms Genetics Genes, Ras Mutation Proto-oncogene Proteins B-raf Proto-oncogene Proteins Ras Proteins Codon Dna Mutational Analysis Genes, Erbb-1 Humans Proto-oncogene Proteins P21(ras) Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Cancer Research |
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