NDLI: Clinical utility of KRAS and BRAF mutations in a cohort of patients with colorectal neoplasms submitted for microsatellite instability testing.

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Clinical utility of KRAS and BRAF mutations in a cohort of patients with colorectal neoplasms submitted for microsatellite instability testing.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cushman-Vokoun, Allison M. Stover, Daniel G. Zhao, Zhiguo Koehler, Elizabeth A. Berlin, Jordan D. Vnencak-Jones, Cindy L.
Description	Country affiliation: United States Author Affiliation: Cushman-Vokoun AM ( Department of Pathology and Microbiology, 985454 Nebraska Medical Center, Omaha, NE 68105-5454, USA. acushman@unmc.edu)
Abstract	BACKGROUND: Molecular analysis has become important in colorectal carcinoma (CRC) evaluation. Alterations in KRAS, BRAF, or mismatch repair (MMR) genes may determine therapeutic response or define a hereditary cancer syndrome. Correlation of DNA studies with clinical findings will further clarify the clinical utility of these markers. PATIENTS AND METHODS: A retrospective study was performed on 111 paraffin-embedded tumor specimens submitted for microsatellite instability (MSI) testing based on clinical history or histologic examination, or both. DNA samples were screened for 7 KRAS mutations and the BRAF p.V600E mutation using fluorescent allele-specific polymerase-chain reaction (PCR) and capillary electrophoresis. Clinical data were collected through chart review. RESULTS: Fifty-eight male and 53 female patients were studied. The incidence of KRAS and BRAF mutations was 49.5% and 7.2%, respectively. Dideoxy sequencing verified KRAS mutation status in 46 of 49 specimens tested. There was a trend toward significance of individual KRAS mutations on survival (P = .003). Dually positive KRAS and MSI tumors exclusively demonstrated p.G12D and p.G13D mutations (G>A transitions). BRAF-mutated tumors were predominantly right-sided and associated with a borderline worse prognosis. Forty-eight percent of tumors with MSI were present in the left colon or rectum. CONCLUSION: Allele-specific PCR is an accurate and convenient method to assess KRAS and BRAF mutations and may detect mutations not identified by dideoxy sequencing. KRAS mutation status, in conjunction with morphologic or clinical parameters, may be useful in determining whether a tumor should be tested for MSI. MSI testing should not be considered exclusively in right-sided lesions. BRAF analysis may not be useful in rectal adenocarcinomas and should be evaluated in larger studies.
File Format	HTM / HTML
ISSN	15330028
e-ISSN	19380674
DOI	10.1016/j.clcc.2013.04.005
Journal	Clinical Colorectal Cancer
Issue Number	3
Volume Number	12
Language	English
Publisher	Elsevier
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Neoplasms Discipline Gastroenterology Tumor Markers, Biological Genetics Colorectal Neoplasms Microsatellite Instability Mutation Proto-oncogene Proteins B-raf Proto-oncogene Proteins Ras Proteins Mortality Pathology Neoplasm Staging Prognosis Proto-oncogene Proteins P21(ras) Retrospective Studies Survival Rate
Content Type	Text
Resource Type	Article
Subject	Gastroenterology Oncology

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