Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20007, USA.
Department of Health Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná 80215-901, Brazil.
Int J Oncol. 2018 Dec;53(6):2745-2757. doi: 10.3892/ijo.2018.4589. Epub 2018 Oct 10.
Breast cancer is the most common and the leading cause of female mortality among South African (SA) women. Several non‑biological and biological risk factors may be attributed to their observed high mortality rate; however, the molecular profiles associated with their breast tumors are poorly characterized. The present study examined the patterns of genome-wide copy number alterations (CNAs) and their potential impact on functional cellular pathways targeted by cancer driver genes in patients with breast cancer from the Western Cape region of SA. Array-comparative genomic hybridization analysis, performed in 28 cases of invasive breast cancer, revealed a mean number of 8.68±6.18 CNAs per case, affecting primarily the Xp22.3 and 6p21-p25 cytobands (57.14% of the cases), followed by 19p13.3-p13.11 (35.7%), 2p25.3-p24.3, 4p16.3-p15.3, 8q11.1-q24.3 and 16 p13.3-p11.2 (32.14%). Functional enrichment analysis of genes and microRNA targets mapped in these affected cytobands revealed critical cancer-associated pathways, including fatty acid biosynthesis and metabolism, extracellular matrix-receptor interaction, hippo and tumor protein p53 signaling pathways, which are regulated by known cancer genes, including CCND1, CDKN1A, MAPK1, MDM2, TP53 and SMAD2. An inverse correlation was observed among the number of CNAs and tumor size and grade; CNAs on the 4p and 6p cytobands were also inversely correlated with tumor grade. No association was observed in the number of CNAs and/or the affected cytobands and the different ethnic groups of the SA patients, indicating that their tumor genome is affected by CNAs, irrespectively of their genetic descent. Additional genomic tumor profiling in SA and other Sub-Saharan African patients with breast cancer is required to determine the associations of the CNAs observed with prognosis and clinical outcome.
乳腺癌是南非（SA）女性中最常见和导致女性死亡的主要原因。一些非生物和生物危险因素可能与她们观察到的高死亡率有关；然而，与她们的乳腺肿瘤相关的分子谱特征描述较差。本研究检查了南非西开普省地区乳腺癌患者中全基因组拷贝数改变（CNAs）的模式及其对癌症驱动基因靶向的功能细胞途径的潜在影响。在 28 例浸润性乳腺癌病例中进行的阵列比较基因组杂交分析显示，每个病例的平均 CNA 数为 8.68±6.18，主要影响 Xp22.3 和 6p21-p25 细胞带（57.14%的病例），其次是 19p13.3-p13.11（35.7%）、2p25.3-p24.3、4p16.3-p15.3、8q11.1-q24.3 和 16p13.3-p11.2（32.14%）。映射到这些受影响细胞带中的基因和 microRNA 靶标的功能富集分析揭示了关键的癌症相关途径，包括脂肪酸生物合成和代谢、细胞外基质-受体相互作用、 Hippo 和肿瘤蛋白 p53 信号通路，这些途径由已知的癌症基因调控，包括 CCND1、CDKN1A、MAPK1、MDM2、TP53 和 SMAD2。CNA 的数量与肿瘤大小和分级呈负相关；4p 和 6p 细胞带的 CNA 也与肿瘤分级呈负相关。在 SA 患者的不同种族群体中，CNA 的数量和/或受影响的细胞带与 CNA 之间没有观察到相关性，这表明他们的肿瘤基因组受到 CNA 的影响，与遗传血统无关。需要在南非和其他撒哈拉以南非洲的乳腺癌患者中进行额外的基因组肿瘤分析，以确定观察到的 CNA 与预后和临床结果的关联。
