Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, New York.
Albert Einstein College of Medicine, Bronx, New York.
Cancer Discov. 2022 May 2;12(5):1282-1293. doi: 10.1158/2159-8290.CD-21-0813.
Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability-high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer (<50 years), AFR and EUR had a similar frequency of MSI-H and tumor mutational burden-high (TMB-H) tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of the diverse U.S. population.
KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC. See related commentary by Eng and Holowatyj, p. 1187. This article is highlighted in the In This Issue feature, p. 1171.
与白人相比，黑人的结直肠癌发病率更高，生存率更差。对 46140 例结直肠腺癌病例进行了综合基因组分析。祖源信息标记物确定了 5301 名非裔患者（AFR）和 33770 名欧洲裔患者（EUR）。AFR 更年轻，微卫星不稳定高（MSI-H）肿瘤较少，KRAS、APC 和 PIK3CA 的改变更为频繁。AFR 出现 KRAS 突变的频率增加，特别是 KRASG12D 和 KRASG13。具有可操作激酶驱动改变（HER2、MET、NTRK、ALK、ROS1 和 RET）的患者比例无差异。在结直肠癌发病年龄较轻（<50 岁）的患者中，AFR 和 EUR 的 MSI-H 和肿瘤突变负荷高（TMB-H）肿瘤的频率相似，但 APC 突变的年龄趋势明显不同，MAPK 通路改变也存在差异。这些发现为治疗决策提供了信息，影响了预后，并强调了需要建立代表美国多样化人群的模型系统。
KRAS（尤其是 KRASG12D/G13）、APC 和 PIK3CA 在 AFR 中改变更频繁，而 MSI-H 肿瘤的频率更低。具有可操作激酶驱动改变的患者比例无差异。在发病年龄较轻的结直肠癌患者中，两种祖源的 MSI-H/TMB-H 肿瘤的频率相似，但 APC 的趋势明显不同。见 Eng 和 Holowatyj 的相关评论，第 1187 页。本文在本期重点介绍中突出显示，第 1171 页。
