Pan-cancer studies of somatic copy number alterations (SCNAs) have demonstrated common SCNA patterns across cancer types, but despite demonstrable differences in aggressiveness of some cancers by race, pan-cancer SCNA variation by race has not been explored. This study investigated a) racial differences in SCNAs in both breast and prostate cancer, b) the degree to which they are shared across cancers, and c) the impact of these shared, race-differentiated SCNAs on cancer survival. Utilizing data from The Cancer Genome Atlas (TCGA), SCNAs were identified using GISTIC 2.0, and in each tumor type, differences in SCNA magnitude between African Americans (AA) and European Americans (EA) were tested using linear regression. Unsupervised hierarchical clustering of the copy number of genes residing in race-differentiated SCNAs shared between tumor types was used to identify SCNA-defined patient groups, and Cox proportional hazards regression was used to test for association between those groups and overall/progression-free survival (PFS). We identified SCNAs that differed by race in breast (n = 58 SCNAs; permutation p < 10− 4) and prostate tumors (n = 78 SCNAs; permutation p = 0.006). Six race-differentiated SCNAs common to breast and prostate found at chromosomes 5q11.2-q14.1, 5q15-q21.1, 8q21.11-q21.13, 8q21.3-q24.3, 11q22.3, and 13q12.3-q21.3 had consistent differences by race across both tumor types, and all six were of higher magnitude in AAs, with the chromosome 8q regions being the only amplifications. Higher magnitude copy number differences in AAs were also identified at two of these race-differentiated SCNAs in two additional hormonally-driven tumor types: endometrial (8q21.3-q24.3 and 13q12.3-q21.3) and ovarian (13q12.3-q21.3) cancers. Race differentiated SCNA-defined patient groups were significantly associated with survival differences in both cancer types, and these groups also differentiated within triple negative breast cancers based on PFS. While the frequency of the SCNA-defined patient groups differed by race, their effects on survival did not. This study identified race-differentiated SCNAs shared by two related cancers. The association of SCNA-defined patient groups with survival demonstrates the clinical significance of combinations of these race-differentiated genomic aberrations, and the higher frequency of these alterations in AA relative to EA patients may explain racial disparities in risk of aggressive breast and prostate cancer.

中文翻译：

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乳腺癌和前列腺癌具有常见的体细胞拷贝数变化，这些变化因种族而异，并且与生存有关。

体癌拷贝数改变（SCNA）的全癌研究表明了不同癌症类型之间的常见SCNA模式，但是尽管某些癌症的种族侵袭性表现出明显差异，但尚未探讨全种族SCNA的变异性。这项研究调查了a）乳腺癌和前列腺癌中SCNA的种族差异，b）它们在癌症中的共享程度，以及c）这些共享的，种族差异的SCNA对癌症生存的影响。利用来自癌症基因组图谱（TCGA）的数据，使用GISTIC 2.0识别了SCNA，并且在每种肿瘤类型中，使用线性回归测试了非洲裔美国人（AA）和欧洲人（EA）之间SCNA大小的差异。肿瘤类型之间共享的种族分化的SCNA中存在的基因拷贝数的无监督分层聚类被用于识别SCNA定义的患者组，而Cox比例风险回归被用于检验这些组与总体/无进展生存之间的关联（PFS）。我们确定了在乳腺癌（n = 58个SCNA；排列p <10-4）和前列腺肿瘤（n = 78个SCNA；排列p = 0.006）中因种族而异的SCNA。在染色体5q11.2-q14.1、5q15-q21.1、8q21.11-q21.13、8q21.3-q24.3、11q22.3和13q12处发现了六个乳腺癌和前列腺癌的种族分化的普通SCNA。 3-q21.3在两种肿瘤类型之间的种族差异均一致，并且所有六种肿瘤的AA含量均较高，其中染色体8q区是唯一的扩增。在另外两种由激素驱动的肿瘤类型中，在其中两种种族分化的SCNA中也发现了更高的AA拷贝数差异：子宫内膜（8q21.3-q24.3和13q12.3-q21.3）和卵巢（13q12）。 3-q21.3）癌症。种族区分的SCNA定义的患者组与两种癌症的生存率差异均显着相关，并且这些组还基于PFS在三阴性乳腺癌中进行了分化。尽管SCNA定义的患者组的频率因种族而异，但它们对生存的影响却没有。这项研究确定了两种相关癌症共有的种族分化的SCNA。SCNA定义的患者群体与生存率的关联证明了这些种族差异的基因组畸变组合的临床意义，