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Genomic aberrations in an African American colorectal cancer cohort reveals a MSI-specific profile and chromosome X amplification in male patients.

Brim H, Lee E, Abu-Asab MS, Chaouchi M, Razjouyan H, Namin H, Goel A, Schäffer AA, Ashktorab H - PLoS ONE (2012)

Bottom Line: Among the 68 CAN genes, all showed some level of alteration in our cohort.Chromosome X amplification in male patients with CRC merits follow-up.The observed CIN may play a distinctive role in CRC in AAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Cancer Center, College of Medicine, Department of Pathology, Howard University, Washington, D.C., United States of America.

ABSTRACT

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.

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Related in: MedlinePlus

Schematic representation of the chromosome 20q13.0-13.3 and break apart amplified DNA includes genes located in this chromosomal region in sporadic African American colorectal cancer patients.
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pone-0040392-g001: Schematic representation of the chromosome 20q13.0-13.3 and break apart amplified DNA includes genes located in this chromosomal region in sporadic African American colorectal cancer patients.

Mentions: Lassmann et al. examined the aberration status of 41 known oncogenes and tumor suppressor genes in CGH data from 22 Caucasians [19]. We compared the outcome of their analysis with our data from African American patients. Overall, the two populations displayed similar aberration profiles for the genes listed in Table 5. However, some differences were noted for the following genes; THRB, RAF1, LPL, DCC, XIST, PCNT, STS, as well as many genes on the 20q12-q13 cytoband (Table 5, Figure 1).


Genomic aberrations in an African American colorectal cancer cohort reveals a MSI-specific profile and chromosome X amplification in male patients.

Brim H, Lee E, Abu-Asab MS, Chaouchi M, Razjouyan H, Namin H, Goel A, Schäffer AA, Ashktorab H - PLoS ONE (2012)

Schematic representation of the chromosome 20q13.0-13.3 and break apart amplified DNA includes genes located in this chromosomal region in sporadic African American colorectal cancer patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412863&req=5

pone-0040392-g001: Schematic representation of the chromosome 20q13.0-13.3 and break apart amplified DNA includes genes located in this chromosomal region in sporadic African American colorectal cancer patients.
Mentions: Lassmann et al. examined the aberration status of 41 known oncogenes and tumor suppressor genes in CGH data from 22 Caucasians [19]. We compared the outcome of their analysis with our data from African American patients. Overall, the two populations displayed similar aberration profiles for the genes listed in Table 5. However, some differences were noted for the following genes; THRB, RAF1, LPL, DCC, XIST, PCNT, STS, as well as many genes on the 20q12-q13 cytoband (Table 5, Figure 1).

Bottom Line: Among the 68 CAN genes, all showed some level of alteration in our cohort.Chromosome X amplification in male patients with CRC merits follow-up.The observed CIN may play a distinctive role in CRC in AAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine and Cancer Center, College of Medicine, Department of Pathology, Howard University, Washington, D.C., United States of America.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus