Abstract B92: Molecular characterization of colorectal cancer in Ghana

Abstract

Abstract Colorectal cancer is the fourth most common cancer in men and the third most common cancer in women worldwide with significant variation between different parts of the globe. Although colorectal cancer incidence is relatively low in West Africa, the most recent publications from Nigeria and Ghana note significant increase of colorectal cancer incidence in these countries since 1970. These studies also show that colorectal cancer in West Africa has distinctive pattern with young age of onset and predominantly left-sided tumors, yet the spectrum of molecular changes in colorectal tumors has not been characterized in West African populations. The goal of this study was to investigate molecular characteristics of colorectal cancer in Ghana. We retrieved 90 formalin-fixed paraffin embedded (FFPE) colorectal cancer blocks from the University of Ghana Medical School (Accra) diagnosed between 1997 and 2007. Ten 5 μm recuts and H&E slide were prepared for each block and reviewed by the pathologist to determine areas of at least 70% tumor cellularity and areas of adjacent normal tissue. DNA was extracted from the microdissected tumor and normal tissue. Only 71 samples had both tumor and normal tissue within the available specimen. Ten microsatellite marker loci (D10S197, BAT26, beta-catenin, D18S58, BAT40, D2S123, D17S250, BAT25, TGF-b-RIIF, and D5S346F) were used for microsatellite instability (MSI) testing using fluorescently labeled primers and fragment analysis. Tumors with at least one mononucleotide marker and a minimum of three available markers were considered for analysis. The tumors with instability in at least 30% of markers were called MSI-High, less than 30% classified as MSI-Low, and tumors with all stable markers were called microsatellite stable (MSS). Sequencing BRAF and KRAS was repeated twice from both directions and analyzed by two independent readers using Sequencher from GeneCodes (Ann Arbor, MI) and Mutation Surveyor from SoftGenetics (State College, PA) to avoid misinterpretation. Out of 71 colorectal cancer pairs of normal and tumor tissue, MSI testing was informative for 70 pairs. An exceptionally large proportion of cancers were MSI-High (29/70, 41.4%), with 14/70 (20%) MSI-Low tumors, and 27/70 (38.6%) MSS tumors. Sequencing of exons 1 and 2 of KRAS in 75 tumors detected 24 (32%) activating mutations (G12D, G12V, G12C, G12S, G13D, Q61R, and Q61K). Surprisingly, the sequencing of exon 15 of BRAF, the location of frequent activating mutation (V600E), did not show any mutations at codons 599 and 600 in 88 tumor samples. Our study showed a very high frequency of MSI-high colorectal tumors (41.4%), consistent with the higher rates of MSI-High cancers observed in some studies of colorectal cancer in African American patients. The frequency of KRAS mutations is comparable to one found in African Americans, but absence of BRAF mutations is intriguing and requires further analysis of the epidemiology and biology of colorectal cancer in West Africa. Citation Format: Leon Raskin, Jonathan C.B. Dakubo, Nicole Palaski, Joel Greenson, Stephen Gruber. Molecular characterization of colorectal cancer in Ghana. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B92.