An integrative CGH, MSI and candidate genes methylation analysis of colorectal tumors.
BACKGROUND
Different DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients.


METHODS
Array 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.


RESULTS
The 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.


CONCLUSIONS
This 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.
Department of Pathology, Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America.
Hassan
H
Brim
Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Mones S
MS
Abu-Asab
Department of Pathology, Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America.
Mehdi
M
Nouraie
Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Jose
J
Salazar
Section of Biomedical Computing, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America.
Jim
J
Deleo
Drexel University College of Medicine, Monmouth Medical Center, Department of Medicine, Long Branch, New Jersey, United States of America.
Hadi
H
Razjouyan
Biochemistry Department, Shiraz University of Medical Sciences, Shiraz, Iran.
Pooneh
P
Mokarram
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
Alejandro A
AA
Schaffer
Biochemistry Department, Shiraz University of Medical Sciences, Shiraz, Iran.
Fakhraddin
F
Naghibhossaini
Department of Pathology, Medicine and Cancer Center, Howard University, College of Medicine, Washington, DC, United States of America.
Hassan
H
Ashktorab
D000704:Analysis of Variance; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007492:Iran; D008297:Male; D046228:Microarray Analysis; D053842:Microsatellite Instability; D010802:Phylogeny
D005819:Genetic Markers