title: Distinct molecular features of colorectal cancer in Ghana.
abstract: OBJECTIVE
  While colorectal cancer (CRC) is common, its incidence significantly varies around the globe. The incidence of CRC in West Africa is relatively low, but it has a distinctive clinical pattern and its molecular characteristics have not been studied. This study is one of the first attempts to analyze molecular, genetic, and pathological characteristics of colorectal cancer in Ghana.
  
  
  METHODS
  DNA was extracted from microdissected tumor and adjacent normal tissue of 90 paraffin blocks of CRC cases (1997-2007) collected at the University of Ghana. Microsatellite instability (MSI) was determined using fragment analysis of ten microsatellite markers. We analyzed expression of mismatch repair (MMR) proteins by immunohistochemistry and sequenced exons 2 and 3 of KRAS and exon 15 of BRAF.
  
  
  RESULTS
  MSI analysis showed 41% (29/70) MSI-High, 20% (14/70) MSI-Low, and 39% (27/70) microsatellite-stable (MSS) tumors. Sequencing of KRAS exons 2 and 3 identified activating mutations in 32% (24/75) of tumors, and sequencing of BRAF exon 15, the location of the common activating mutation (V600), did not show mutations at codons 599 and 600 in 88 tumors.
  
  
  CONCLUSIONS
  Our study found a high frequency of MSI-High colorectal tumors (41%) in Ghana. While the frequency of KRAS mutations is comparable with other populations, absence of BRAF mutations is intriguing and would require further analysis of the molecular epidemiology of CRC in West Africa.
authors: Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, United States. leonid.raskin@vanderbilt.edu
authors: Leon
authors: L
authors: Raskin
authors: Jonathan C B
authors: JC
authors: Dakubo
authors: Nicole
authors: N
authors: Palaski
authors: Joel K
authors: JK
authors: Greenson
authors: Stephen B
authors: SB
authors: Gruber
mesh_terms: D001741:Black or African American / Q000235:genetics; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D005091:Exons; D005260:Female; D011905:Genes, ras; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D017720:Molecular Epidemiology; D016612:Paraffin Embedding; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Colorectal cancer; Ghana; MSI; Microsatellite instability; West Africa
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