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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

A schematic cladogram from a parsimony phylogenetic analysis of the aCGH data from the 30 CRC tumors.NC: No Changes, C: Changes, N: number of samples in cluster-The other digit within the clusters correspond to node numbers.
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pone-0040392-g002: A schematic cladogram from a parsimony phylogenetic analysis of the aCGH data from the 30 CRC tumors.NC: No Changes, C: Changes, N: number of samples in cluster-The other digit within the clusters correspond to node numbers.

Mentions: A maximum parsimony phylogenetic analysis was conducted on the CGH data through MIX algorithm (of the PHYLIP analytical package [25]) to produce the phylogenetic cladogram. The generated cladogram branched into two main clades and the partition and further subdivisions into clusters are summarized schematically in Figure 2. One clade included 22 patients (right-sided CRC: 63%; male: 50%; higher stage [>2]: 59%) that included all MSI-H samples. The other clade included 8 patients (right-sided CRC: 87%; male: 50%; higher stage >2: 71%, all were non-MSI. The first clade of 22 patients was further divided into two smaller groups with 14 (right sided CRC: 57%; male: 43%; higher stage [>2]: 43%) and 8 (right sided CRC: 75%; male: 62%; higher stage [>2]: 87%, p = 0.04) patients. It is noteworthy that 80% (4/5) of MSI-H tumors grouped together within the 14 patients' clade (Figure 2). All of these tumors have a very low number of aberrations (<15). The only MSI-H tumor that did not cluster with the others have a high number of aberrations (63) and as such, was most likely driven by chromosomal instability rather than by microsatellite instability.


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)

A schematic cladogram from a parsimony phylogenetic analysis of the aCGH data from the 30 CRC tumors.NC: No Changes, C: Changes, N: number of samples in cluster-The other digit within the clusters correspond to node numbers.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0040392-g002: A schematic cladogram from a parsimony phylogenetic analysis of the aCGH data from the 30 CRC tumors.NC: No Changes, C: Changes, N: number of samples in cluster-The other digit within the clusters correspond to node numbers.
Mentions: A maximum parsimony phylogenetic analysis was conducted on the CGH data through MIX algorithm (of the PHYLIP analytical package [25]) to produce the phylogenetic cladogram. The generated cladogram branched into two main clades and the partition and further subdivisions into clusters are summarized schematically in Figure 2. One clade included 22 patients (right-sided CRC: 63%; male: 50%; higher stage [>2]: 59%) that included all MSI-H samples. The other clade included 8 patients (right-sided CRC: 87%; male: 50%; higher stage >2: 71%, all were non-MSI. The first clade of 22 patients was further divided into two smaller groups with 14 (right sided CRC: 57%; male: 43%; higher stage [>2]: 43%) and 8 (right sided CRC: 75%; male: 62%; higher stage [>2]: 87%, p = 0.04) patients. It is noteworthy that 80% (4/5) of MSI-H tumors grouped together within the 14 patients' clade (Figure 2). All of these tumors have a very low number of aberrations (<15). The only MSI-H tumor that did not cluster with the others have a high number of aberrations (63) and as such, was most likely driven by chromosomal instability rather than by microsatellite instability.

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