Genomic Aberrations in an African American Colorectal Cancer Cohort Reveals a MSI-Specific Profile and Chromosome X Amplification in Male Patients
Autor: | Alejandro A. Schäffer, Hassanzadeh Namin, Mones Abu-Asab, Ajay Goel, Hassan Brim, Hadi Razjouyan, Hassan Ashktorab, Mohamed Chaouchi, Edward L. Lee |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Oncology
Male Colorectal cancer Microarrays Chromosomes Human Pair 20 lcsh:Medicine Cohort Studies Chromosomal Disorders 0302 clinical medicine Chromosome instability Gene duplication Gastrointestinal Cancers lcsh:Science X chromosome Phylogeny Genetics 0303 health sciences Comparative Genomic Hybridization Multidisciplinary Colon Adenocarcinoma virus diseases Chromosomal Deletions and Duplications Middle Aged female genital diseases and pregnancy complications 3. Good health 030220 oncology & carcinogenesis Medicine Female Microsatellite Instability Colorectal Neoplasms Research Article medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Gastroenterology and Hepatology Carcinoid Tumor Biology White People 03 medical and health sciences Internal medicine Gastrointestinal Tumors medicine Humans neoplasms 030304 developmental biology Aged Demography Clinical Genetics Chromosome Aberrations Chromosomes Human X Genome Human lcsh:R Gene Amplification Microsatellite instability Computational Biology Cancers and Neoplasms medicine.disease Human genetics digestive system diseases Black or African American Human genome lcsh:Q Comparative genomic hybridization Genes Neoplasm |
Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 8, p e40392 (2012) |
ISSN: | 1932-6203 |
Popis: | Objective DNA aberrations that cause colorectal cancer (CRC) occur in multiple steps that involve microsatellite instability (MSI) and chromosomal instability (CIN). Herein, we studied CRCs from AA patients for their CIN and MSI status. Experimental Design Array CGH was performed on 30 AA colon tumors. The MSI status was established. The CGH data from AA were compared to published lists of 41 TSG and oncogenes in Caucasians and 68 cancer genes, proposed via systematic sequencing for somatic mutations in colon and breast tumors. The patient-by-patient CGH profiles were organized into a maximum parsimony cladogram to give insights into the tumors' aberrations lineage. Results The CGH analysis revealed that CIN was independent of age, gender, stage or location. However, both the number and nature of aberrations seem to depend on the MSI status. MSI-H tumors clustered together in the cladogram. The chromosomes with the highest rates of CGH aberrations were 3, 5, 7, 8, 20 and X. Chromosome X was primarily amplified in male patients. A comparison with Caucasians revealed an overall similar aberration profile with few exceptions for the following genes; THRB, RAF1, LPL, DCC, XIST, PCNT, STS and genes on the 20q12-q13 cytoband. Among the 68 CAN genes, all showed some level of alteration in our cohort. Conclusion Chromosome X amplification in male patients with CRC merits follow-up. The observed CIN may play a distinctive role in CRC in AAs. The clustering of MSI-H tumors in global CGH data analysis suggests that chromosomal aberrations are not random. |
Databáze: | OpenAIRE |
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