Abstract
BackgroundDifferent DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients.Materials and MethodsArray CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established.ResultsThe number of aberrations seem to depend on the MSI status. MSI-H tumors displayed the lowest number of aberrations. MSP revealed that most markers were methylated, except RNF182 gene. P16 and MLH1 genes were primarily methylated in MSI-H tumors. Seven markers with moderate to high frequency of methylation (SYNE1, MMP2, CD109, EVL, RET, LGR and PTPRD) had very low levels of chromosomal aberrations. All chromosomes were targeted by aberrations with deletions more frequent than amplifications. The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53. Aberrations targeting chromosome X were primarily amplifications in male patients and deletions in female patients. A finding similar to what we reported for African American CRC patients.ConclusionThis first comprehensive analysis of CRC Iranian tumors reveals a high MSI rate. The MSI tumors displayed the lowest level of chromosomal aberrations but high frequency of methylation. The MSI-L were predominantly targeted with chromosomal instability in a way similar to the MSS tumors. The global chromosomal aberration profiles showed many similarities with other populations but also differences that might allow a better understanding of CRC's clinico-pathological specifics in this population.
Highlights
Different DNA aberrations processes can cause colorectal cancer (CRC)
A finding similar to what we reported for African American CRC patients
The microsatellite instability (MSI)-L were predominantly targeted with chromosomal instability in a way similar to the microsatellite stable (MSS) tumors
Summary
Different DNA aberrations processes can cause colorectal cancer (CRC). We conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients. Several studies have investigated the genetic and epigenetic events underlying the development of colorectal cancer (CRC). This is one of the world’s leading common cancers [1]. Its incidence is different depending on the geographical and ethnic backgrounds. African-Americans, for example have the highest incidence of the disease in the US and have very high incidence when compared to their African counterparts with whom they share the same genetic background [2,3,4]. Most CRCs arise from adenomas, in a process described as adenoma-carcinoma sequence [5]. The initiation and progression of CRC is associated with alterations in the function of oncogenes and tumor suppressor genes
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