Barcelona Institute for Global Health, ISGlobal, Doctor Aiguader 88, 08003, Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Hum Genomics. 2019 Nov 21;13(1):57. doi: 10.1186/s40246-019-0242-2.
Chromosomal inversions are structural genetic variants where a chromosome segment changes its orientation. While sporadic de novo inversions are known genetic risk factors for cancer susceptibility, it is unknown if common polymorphic inversions are also associated with the prognosis of common tumors, as they have been linked to other complex diseases. We studied the association of two well-characterized human inversions at 17q21.31 and 8p23.1 with the prognosis of lung, liver, breast, colorectal, and stomach cancers.
Using data from The Cancer Genome Atlas (TCGA), we observed that inv8p23.1 was associated with overall survival in breast cancer and that inv17q21.31 was associated with overall survival in stomach cancer. In the meta-analysis of two independent studies, inv17q21.31 heterozygosity was significantly associated with colorectal disease-free survival. We found that the association was mediated by the de-methylation of cg08283464 and cg03999934, also linked to lower disease-free survival.
Our results suggest that chromosomal inversions are important genetic factors of tumor prognosis, likely affecting changes in methylation patterns.
染色体倒位是一种结构遗传变异，其中染色体片段改变了其方向。虽然散发性新生倒位是癌症易感性的已知遗传风险因素，但目前尚不清楚常见的多态性倒位是否也与常见肿瘤的预后有关，因为它们与其他复杂疾病有关。我们研究了两个特征明确的人类倒位 17q21.31 和 8p23.1 与肺癌、肝癌、乳腺癌、结直肠癌和胃癌预后的关系。
我们利用癌症基因组图谱（TCGA）的数据，观察到 inv8p23.1 与乳腺癌的总生存率有关，而 inv17q21.31 与胃癌的总生存率有关。在两项独立研究的荟萃分析中，inv17q21.31 杂合性与结直肠癌无病生存率显著相关。我们发现，这种关联是由 cg08283464 和 cg03999934 的去甲基化介导的，这也与较低的无病生存率有关。
我们的结果表明，染色体倒位是肿瘤预后的重要遗传因素，可能影响甲基化模式的变化。
