| BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. | |
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MedLine Citation:
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PMID: 22228154 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Colorectal cancer is a heterogeneous disease with multiple underlying genetic mutations causing different clinical phenotypes. Mutation in the BRAF oncogene is a key step in malignant transformation within the methylator pathway to colorectal cancer. However, there is a paucity of information about BRAF mutant colorectal tumors. OBJECTIVE: This study defines the clinical characteristics and oncologic outcome associated with colorectal cancer BRAF mutations. DESIGN: Colorectal adenocarcinomas from a single-institution frozen-tumor biobank were studied. Genomic DNA was isolated and analyzed for mutations in the BRAF oncogene by polymerase chain reaction amplification followed by direct sequencing. A sample was classified as mutant if any of the tested loci were mutated. Patient and tumor characteristics were recorded including patient age, sex, tumor location, tumor differentiation, and microsatellite instability. MAIN OUTCOME MEASURES: Statistical associations with BRAF mutant tumors were determined by the Fisher exact probability test, χ test, or Wilcoxon analysis. Kaplan-Meier estimates and multivariate Cox regression analysis were performed for overall survival. RESULTS: Four hundred seventy-five colorectal adenocarcinomas were included in the study population; 56 samples harbored a BRAF mutation (12%). There were significant differences between BRAF wild-type and mutant tumors in age (66 vs 75 years, p = 0.004), female sex (44% vs 71%, p < 0.001), proximal tumor location (44% vs 95%, p < 0.001), and frequency of microsatellite instability (16% vs 76%, p < 0.001). There was no difference in cancer stage between BRAF mutant and wild-type populations. Survival data were analyzed for 322 patients with stage I to III disease, and patients with a BRAF mutation had decreased overall survival than those without a mutation (p = 0.018). With the use of Cox regression analysis, BRAF mutation conferred a worse overall survival (HR 1.79, CI 1.05-3.05, p = 0.03) independent of microsatellite instability status. CONCLUSIONS: BRAF mutations in colorectal cancers are associated with distinct clinical characteristics and worse prognosis. |
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Authors:
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Matthew F Kalady; Kathryn L Dejulius; Julian A Sanchez; Awad Jarrar; Xiuli Liu; Elena Manilich; Marek Skacel; James M Church |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Diseases of the colon and rectum Volume: 55 ISSN: 1530-0358 ISO Abbreviation: Dis. Colon Rectum Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-09 Completed Date: 2012-03-07 Revised Date: 2012-06-21 |
Medline Journal Info:
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Nlm Unique ID: 0372764 Medline TA: Dis Colon Rectum Country: United States |
Other Details:
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Languages: eng Pagination: 128-33 Citation Subset: IM |
Affiliation:
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Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. kaladym@ccf.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
/
diagnosis,
genetics*,
mortality Adolescent Adult Age Factors Aged Aged, 80 and over Colorectal Neoplasms / diagnosis, genetics*, mortality DNA Mutational Analysis Female Humans Kaplan-Meier Estimate Microsatellite Instability Middle Aged Mutation* Polymerase Chain Reaction Prognosis Proportional Hazards Models Proto-Oncogene Proteins B-raf / genetics* Retrospective Studies Sex Factors Young Adult |
| Chemical | |
Reg. No./Substance:
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EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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