Departamento de Genética, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Departamento Básico de Medicina, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Mol Oncol. 2021 Feb;15(2):473-486. doi: 10.1002/1878-0261.12842. Epub 2020 Nov 19.
Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non-invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome-wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case-control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well-characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer-related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof-of-concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.
人类的多样性是开发稳健的全球肿瘤生物标志物的主要障碍之一。人类群体中的表观遗传变异性与不同的遗传背景、不同的生活方式和环境暴露有关，这些都应该进行研究。为了在乌拉圭人群中鉴定散发性乳腺癌的潜在非侵入性生物标志物，我们在 22 名散发性乳腺癌女性和 10 名健康女性的白细胞中使用 Illumina 甲基化芯片进行了全基因组 DNA 甲基化研究，开展了病例对照研究。我们描述了一个由 38 个差异甲基化 CpG 位置组成的面板，该面板能够对乳腺癌患者（BCP）和对照组进行聚类，并且还重现了 12 个原发性乳腺癌及其匹配的正常乳腺组织中的甲基化差异。在此基础上，我们简化了检测方法，以提高其在临床环境中的适用性，并使用 80 个 BCP 和 80 个健康对照的白细胞 DNA 样本的独立、特征明确的队列来验证特定癌症相关基因的甲基化结果。我们的研究鉴定了 CYFIP1 处的甲基化作为乌拉圭人群中散发性乳腺癌的新型表观遗传生物标志物候选物。这些结果为设计针对拉丁美洲人群的生物标志物面板的更大规模研究提供了概念验证。
