Decreased copy-neutral loss of heterozygosity in African American colorectal cancers.

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While previous studies have found that copy number variations (CNVs) occur at similar frequency in African American and White CRCs, copy-neutral loss of heterozygosity (cnLOH) has not been investigated. In the present study, we used publicly available data from The Cancer Genome Atlas (TCGA) as well as data from an African American CRC cohort, the Chicago Colorectal Cancer Consortium (CCCC), to compare frequencies of CNVs and cnLOH events in CRCs in the two racial groups. Using genotype microarray data, we analyzed large-scale CNV and cnLOH events from 166 microsatellite stable CRCs-31 and 39 African American CRCs from TCGA and the CCCC, respectively, and 96 White CRCs from TCGA. As reported previously, the frequencies of CNVs were similar between African American and White CRCs; however, there was a significantly lower frequency of cnLOH events in African American CRCs compared to White CRCs, even after adjusting for demographic and clinical covariates. Although larger differences for chromosome 18 were observed, a lower frequency of cnLOH events in African American CRCs was observed for nearly all chromosomes. These results suggest that mechanistic differences, including differences in the frequency of cnLOH, could contribute to clinicopathological disparities between African Americans and Whites. Additionally, we observed a previously uncharacterized phenomenon we refer to as small interstitial cnLOH, in which segments of chromosomes from 1 to 5 Mb long were affected by cnLOH.", "claims": [{"id": "claim-method", "statement": "Linear regression models were used to determine associations between the number of chromosome arms affected by cnLOH in an individual and covariates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32293075", "locator": "sections[6] \"Statistical Analyses\" paragraph 2", "quote": "Linear regression models were used to determine associations between the number of chromosome arms affected by cnLOH in an individual and covariates."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data availabilityThe data that support the findings of this study are available from TCGA. Restrictions apply to the availability of these data, which were used under license for this study. 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The data from the Chicago Colorectal Cancer Consortium part of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Copy-neutral loss of heterozygosity events were significantly less frequent in African American CRCs than in White CRCs.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "Chromosome arms in CCCC African American CRCs, TCGA African American CRCs, and combined African American CRCs were affected at a frequency of 2.6%, 6.5%, and 4.3%, respectively, whereas 11.8% of chromosome arms of White CRCs were affected by cnLOH (Figure 2, Supplementary Table 4, p < 0.001 for all comparisons)."}, "evidence": [{"asset": "source:pmid:32293075", "locator": "sections[9] \"White CRCs have a higher frequency of cnLOH than African American CRCs for most chromosome arms\" paragraph 2", "quote": "Chromosome arms in CCCC African American CRCs, TCGA African American CRCs, and combined African American CRCs were affected at a frequency of 2.6%, 6.5%, and 4.3%, respectively, whereas 11.8% of chromosome arms of White CRCs were affected by cnLOH (Figure 2, Supplementary Table 4, p < 0.001 for all comparisons)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Copy-neutral loss of heterozygosity events were significantly less frequent in African American CRCs than in White CRCs.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32293075"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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